Helper Effect Research Articles

The relationship between serum interleukin-1β and circulating CD16+ neutrophils for assessing progression-free time in advanced ovarian cancer

BACKGROUND: Ovarian cancer is the most aggressive gynecological tumor with high mortality. The ambivalent, both helper and suppressive effects of neutrophils on the cells of innate and adaptive immunity determines their important immunoregulatory role in the development of malignant tumors. AIM: Evaluation of the effect of serum interleukin-1β and circulating neutrophils CD16+ on progression-free time in advanced ovarian cancer. MATERIAL AND METHODS: In 42 primary patients with serous ovarian adenocarcinoma (median age 54 years) with ascites and 15 patients with benign ovarian tumors (median age 60 years) admitted for examination and treatment to the Regional Clinical Oncology Dispensary before receiving neoadjuvant antitumor treatment (2015–2020), the level of interleukin-1β in the blood serum was determined using enzyme immunoassay, and the number of CD16+ neutrophils was determined by fluorescence microscopy using monoclonal antibodies. Statistical processing was performed using Statistica 13 and Jamovi 2.4.14 programs. Progression-free time analysis of patients was performed using the Cox and Kaplan–Meier regression methods. RESULTS: It was found that the number of circulating CD16+ neutrophils in advanced ovarian cancer with ascites was lower than in benign ovarian tumors [48.0; 95% confidence interval (CI) 46.59–48.12 versus 50.0; 95% CI 48.51–49.76; p=0.017]. At the same time, the level of interleukin-1β in the blood serum in advanced ovarian cancer with ascites was higher than in benign ovarian tumors [2.52 (95% CI 2.50–3.37) versus 1.26 (95% CI 0.97–1.55) (p=0.0001)]. In multivariate Cox analysis in patients with ascites (odds ratio 4.334; 95% CI 1.83–10.23; p=0.001), both the CD16+ neutrophil count (odds ratio 0.73; 95% CI 0.62–0.86; p=0.0001) and serum interleukin-1β levels (odds ratio 1.90; 95% CI 1.41–2.57; p=0.0001) had prognostic significance for assessing progression-free time. CONCLUSION: The number of circulating CD16+ neutrophils and serum interleukin-1β levels simultaneously affect progression-free time in advanced ovarian cancer.

Progress of IL-21 and Tfh Mediated Immunotherapy in Non-small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is a prevalent and aggressive global malignancy. Conventional surgical treatments, radiotherapy, chemotherapy, and targeted therapies often fall short in halting disease progression due to inherent limitations, resulting in suboptimal prognosis. Despite the advent of immunotherapy drugs offering new hope for NSCLC treatment, current efficacy remains insufficient to meet all patient needs. Therefore, actively exploring novel immunotherapeutic approaches to further reduce mortality rates in NSCLC patients has become a crucial focus of NSCLC research. This article aims to systematically review the anti-tumor effects of interleukin-21 and follicular helper T cells in NSCLC immunotherapy by summarizing and analyzing relevant literatures from both domestic and international sources, as well as exploring the potential for enhancing NSCLC treatment prospects through immune checkpoint regulation via immunotherapeutic means. .

Effects of bovine ova density and culture supplements on cleavage and blastocyst development rates of in vitro embryos

An optimized in vitro culture system is important to maximize bovine blastocyst development. Four experiments were conducted to explore manipulation of culture environments and investigate the benefits of culturing embryos in groups. Follicles were aspirated from abattoir-derived ovaries and selected oocytes were matured, fertilized, vortexed, and randomly placed in culture groups. Experiment 1 evaluated the effects of ova culture density on blastocyst development among embryos cultured individually or in groups of 5, 10, 20, or 50 embryos. Experiment 2 evaluated the effects of conditioned media from previous replicates on embryo development of the current culture. In Experiment 3, cleaved embryos were grouped together after being in culture for 24 hours. Lastly, in Experiment 4, grouped embryos were placed in 10 μl culture drops to evaluate the effect of high density/low media volume on development. Cleavage and blastocyst rates analyzed via Chi-square indicated that although cleavage rates were similar among culture groups (and experiments), blastocyst development was lower (p < 0.05) in 1 embryo culture group compared to other groups. When conditioned culture media from previous replicates were added to original culture media, blastocyst development was similar among original and conditioned culture groups of 20 and 50 embryos. When cleaved embryos were amalgamated and cultured, blastocyst development was higher (p < 0.05) in culture groups of 10 than 1 cleaved embryo groups but similar to controls for both culture groups. When embryos were cultured in 10 μl drops, embryos cultured in groups of 5 had lower development to blastocysts compared to groups of 2, 10, 25, and control. In conclusion, these data indicated an apparent ‘helper effect’ expressed in culture environments of groups, and this effect apparently occurred after cleavage but before blastocyst development. Direct or indirect role(s) that additional cells have on in vitro culture and the mechanism of this helper effect requires further investigation.

Egg components and offspring survival vary with group size and laying order in a cooperative breeder

Prenatal resource allocation to offspring can be influenced by maternal environment and offspring value, and affect offspring survival. An important pathway for flexible maternal allocation is via egg components such as nutrients and hormones. In cooperative breeders, females with helpers may increase resource allocation to eggs—‘differential allocation’—or reduce it—‘load-lightening’. Yet, helper effects on egg composition have been poorly studied. Moreover, it is unknown how helpers’ presence modulates laying order effects on egg content and survival. Here, we investigated how maternal allocation varied with group size and laying order in the cooperatively breeding sociable weaver (Philetairus socius). We estimated interactive effects of helpers and laying order on allocation to egg mass, yolk nutrients—yolk mass, proteins, lipids, carotenoids, vitamin A and vitamin E—and hormones—testosterone, androstenedione, and corticosterone. Results concurred with the ‘differential allocation’ predictions. Females with more helpers produced later-laid eggs with heavier yolks and more lipids, and laid eggs overall richer in lipids. Proteins, antioxidants, and hormones were not found to vary with helper number. We then analyzed how helper number modulated laying order effects on survival. Females with more helpers did not specifically produce later-laid eggs with higher survival, but eggs laid by females with more helpers were overall more likely to fledge. These findings show that some egg components (yolk mass, lipids) can positively vary according to females’ breeding group size, which may improve offspring fitness.

Evidence of a load-lightening helper effect in Florida Scrub-Jays: implications for translocation

Evidence of a load-lightening helper effect in Florida Scrub-Jays: implications for translocation

Clinical Characteristics and Potential Mechanisms in Patients with Abnormal Liver Function Indices and Elevated Serum IgG4.

We analyzed the etiological classification and clinical characteristics of patients with abnormal liver function indices and elevated serum IgG4 levels and investigated the effects of intrahepatic follicular helper T cell (Tfh) infiltration and serum IL-21. Clinical data (age, sex, past history, clinical manifestations, laboratory tests, imaging, diagnosis, and treatment) and etiology of liver injury from 136 patients were analyzed. We compared the general condition, clinical characteristics, and laboratory tests of 19 AIH (autoimmune hepatitis) patients with elevated serum IgG4 levels with those of 20 AIH patients with normal serum IgG4 levels admitted at the same time. Five patients with AIH and elevated serum IgG4 levels and five AIH patients with normal IgG4 levels were matched by sex, age, and liver function, and Tfh infiltration in liver biopsy tissues of patients in both groups was determined by immunofluorescence staining. Five AIH patients with elevated serum IgG4 levels were selected for measurement of serum interleukin-21 (IL-21) levels by enzyme-linked immunosorbent assay (ELISA), seventeen AIH patients with normal serum IgG4 were matched by sex, age, and liver function indices, and 29 physically healthy individuals matched by sex and age were selected as the control group. The changes in patients with IgG4-RD and abnormal liver function before and after glucocorticoid treatment were measured. Patients (136) with abnormal liver function indices and elevated serum IgG4 levels were diagnosed with liver disease of different etiologies. IgG4-related disease was the most frequent, followed by AIH and malignancy. Abnormal liver function indices with high serum IgG4 were most commonly seen as elevated gamma glutamyl transferase (GGT). The AIH group with elevated serum IgG4 had increased intrahepatic levels of Tfh. IL-21 in AIH patients with elevated IgG4 was higher than in patients with normal IgG4 and healthy controls. Patients (n = 28) with abnormal liver function indices and IgG4-related disease received glucocorticoid therapy for six months, and ALT, AST, ALKP, GGT, TBil, DBil, IgG, IgG4, and IgE were significantly lower after treatment. Elevated serum IgG4 was seen in patients with abnormal liver function indices with diverse causes. Tfh infiltration and increased IL-21 production may be related to the pathogenesis of AIH with elevated serum IgG4. Glucocorticoid therapy is effective in patients with abnormal liver function indices and IgG4-related disease. Assessing immune function in patients with abnormal liver function indices and elevated serum IgG4 levels should facilitate diagnosis and treatment of the disease.

Prenatal Rejecter NK Cells Enhance Allo-specific Th17/Tc17 Cell Responses via TGF-beta1, IL-6 and GM-CSF.

Abstract In utero hematopoietic cellular transplantation (IUHCT) has the potential to treat congenital benign cellular disease without chemotherapy or radiation. Prenatal tolerance is essential in this regard. Previous studies involving prenatally created chimeras have shown that immunologically tolerant NK cells (friendly, fNK) from engrafter mice suppress allo Tc1 responses, while intolerant NK cells (hostile, hNK) from rejecter mice enhance allo Tc1 responses. Given that Th17 cells are also involved in allograft rejection, we sought to determine if rejecter hNK cells induce/expand allo-specific Th17/Tc17 cells. We examined the helper potential of prenatally educated hNK cells in non-tolerant prenatal Balb/c --- > B6.Thy1.2 rejecter chimeras. Naïve Thy1.1+ responder T cells and allogenic target cells were adoptively transferred into rejecter or naïve hosts that had been depleted of endogenous T cells and fNK cells. We found increased Th17/Tc17 alloimmunity in the responder Thy1.1+T cell population in rejecters when compared to naïve hosts. Additionally, through ELISPOT, we confirmed increased IL-17A production by responder T cells when co-cultured with allo-specific hNK cells from rejecter mice. Hostile NK cells from rejecter mice produce higher levels of Th17 driving cytokines, TGF-beta 1, IL-6 and GM-CSF when compared to naïve hNK. From these results, we conclude that prenatal rejecter hNK cells have an enhanced helper effect on Th17/Tc17 alloimmunity in vivo and in vitro. These findings support an evolving paradigm that prenatally educated NK cell can regulate the balance between Th1/Th17 and Treg functions. Supported by NIH R01HL103745 Lurie Children’s Hospital Research Foundation (to A.F.S.)

Filter Plating Method for Rendering Picocyanobacteria Cultures Free of Heterotrophic Bacterial Contaminants and Clonal.

Isolates of the marine picocyanobacteria, Prochlorococcus and Synechococcus, are often accompanied by diverse heterotrophic “contaminating” bacteria, which can act as confounding variables in otherwise controlled experiments. Traditional microbiological methods for eliminating contaminants, such as direct streak-plating, are often unsuccessful with this particular group of microorganisms. While they will grow in pour plates, colonies often remain contaminated with heterotrophic bacteria that can migrate through the soft agar. Additionally, axenic clones of picocyanobacteria can be recovered via dilution-to-extinction in liquid medium, but the efficiency of recovery is low, often requiring large numbers of 96-well plates. Here, we detail a simple and effective protocol for rendering cultures of Synechococcus and Prochlorococcus strains free of bacterial contaminants while at the same time yielding clonal isolates. We build on the fact that co-culture with specific heterotrophs—“helper heterotrophs”—is often necessary to grow colonies of picocyanobacteria from single cells in agar. Suspecting that direct physical contact between the helper and the picocyanobacterial cells was not necessary for the “helper effect,” we developed a protocol in which the helper cells are embedded in soft agar pour plates, a filter overlaid on the surface, and a picocyanobacterial culture is diluted and then spotted on top of the filter. With this approach, motile contaminants cannot swim to the colonies, and it is possible to obtain the expected number of colonies from a given input (i.e., a Poisson distribution of colonies with an expected value equal to the input number of cells), thus ensuring clonal colonies. Using this protocol, we rendered three strains of Synechococcus, two strains of Prochlorococcus, and 19 new strains of Synechococcus from coastal seawater clonal and free of heterotrophic bacteria. The simplicity of this approach should expand the repertoire of axenic picocyanobacterial strains available for controlled physiological experiments. It will also enable the study of microdiversity in populations of picocyanobacteria by facilitating large-scale isolation of picocyanobacterial clones from a single source, including direct isolation from natural seawater.

Revealing the Complexity of Sweepovirus-Deltasatellite-Plant Host Interactions: Expanded Natural and Experimental Helper Virus Range and Effect Dependence on Virus-Host Combination.

Sweepoviruses are begomoviruses (genus Begomovirus, family Geminiviridae) with ssDNA genomes infecting sweet potato and other species of the family Convolvulaceae. Deltasatellites (genus Deltasatellite, family Tolecusatellitidae) are small-size non-coding DNA satellites associated with begomoviruses. In this study, the genetic diversity of deltasatellites associated with sweepoviruses infecting Ipomoea indica plants was analyzed by further sampling the populations where the deltasatellite sweet potato leaf curl deltasatellite 1 (SPLCD1) was initially found, expanding the search to other geographical areas in southern continental Spain and the Canary Islands. The sweepoviruses present in the samples coinfected with deltasatellites were also fully characterized by sequencing in order to define the range of viruses that could act as helper viruses in nature. Additionally, experiments were performed to assess the ability of a number of geminivirids (the monopartite tomato leaf deformation virus and the bipartite NW begomovirus Sida golden yellow vein virus, the bipartite OW begomovirus tomato leaf curl New Delhi virus, and the curtovirus beet curly top virus) to transreplicate SPLCD1 in their natural plant hosts or the experimental host Nicotiana benthamiana. The results show that SPLCD1 can be transreplicated by all the geminivirids assayed in N. benthamiana and by tomato leaf curl New Delhi virus in zucchini. The presence of SPLCD1 did not affect the symptomatology caused by the helper viruses, and its effect on viral DNA accumulation depended on the helper virus–host plant combination.

Contrasting associations between nestling telomere length and pre and postnatal helpers' presence in a cooperatively breeding bird.

Studies on cooperative breeders have addressed the effects of non-breeding 'helpers' on reproduction and parental care, but the consequences for offspring physiology and long-term survival are less understood. Helpers are expected to benefit offspring, but their presence can also lead to decreased pre- or post-natal parental reproductive effort. To examine whether prenatal and postnatal helpers influence offspring condition, we conducted a whole-clutch cross-fostering experiment in sociable weavers (Philetairus socius) that altered the nestlings' social environment (presence/absence of helpers). We tested whether relative telomere length (rTL), an indicator of somatic maintenance, was influenced by prenatal and/or postnatal presence of helpers 9 and 17days after hatching, and whether rTL predicted long-term survival. Nine days after hatching, we found an overall positive effect of postnatal helpers on rTL: for nestlings with prenatal helpers, a reduction in the number of helpers post-hatch was associated with shorter telomeres, while nestlings swapped from nests without helpers to nests with helpers had a larger rTL. However, when prenatal helpers were present, an increased number of helpers after hatching led to shorter telomeres. Nine-day old chicks with longer rTL tended to be more likely to survive over the 5years following hatching. However, close to fledging, there was no detectable effect of the experiment on rTL and no link between rTL and survival. This experimental study of a wild cooperative breeder, therefore, presents partial support for the importance of the presence of helpers for offspring rTL and the link between early-life telomere length and long-term survival.

Complex effects of helper relatedness on female extrapair reproduction in a cooperative breeder

AbstractIn cooperatively breeding species, the presence of male helpers in a group often reduces the breeding female’s fidelity to her social partner, possibly because there is more than one potential sire in the group. Using a long-term study of cooperatively breeding superb fairy-wrens (Malurus cyaneus) and records of paternity in 1936 broods, we show that the effect of helpers on rates of extrapair paternity varied according to the helpers’ relatedness to the breeding female. The presence of unrelated male helpers in a group increased average rates of extrapair paternity, from 57% for groups with no unrelated helpers, to 74% with one unrelated helper, to 86% with 2+ unrelated helpers. However, this increase was due in equal part to helpers within the group and males in other groups achieving increased paternity. In contrast, helpers who were sons of the breeding female did not gain paternity, nor did they affect the level of extra-group paternity (which occurred at rates of 60%, 58%, 61% in the presence of 0, 1, 2+ helper sons, respectively). There was no evidence of effects of helpers’ relatedness to the female on nest productivity or nestling performance. Because the presence of helpers per se did not elevate extrapair reproduction rates, our results undermine the “constrained female hypothesis” explanation for an increase in extrapair paternity with helper number in cooperative breeders. However, they indicate that dominant males are disadvantaged by breeding in “cooperative” groups. The reasons why the presence of unrelated helpers, but not of helper-sons, results in higher rates of extra-group reproduction are not clear.

Maternal allocation in relation to weather, predation and social factors in a colonial cooperative bird

Females may adjust prenatal allocation in relation to ecological conditions that affect reproductive success, such as weather conditions or predation risk. In cooperative breeders, helpers might also influence reproductive success, and previous studies suggest that females can lay smaller eggs or larger clutches when breeding with more helpers. Although recent work suggests that helper effects can vary according to climatic variables, how social and ecological factors interact to shape prenatal allocation is poorly understood. Here, we examine how ecological and social components of the breeding environment covary with egg mass and clutch size, using as a model the sociable weaver Philetairus socius, a colonial, cooperatively breeding passerine. The study spanned 9years and included over 1,900 eggs from over 550 clutches. Our analyses combined natural variation in weather conditions (rainfall before each reproductive event) with a nest predator-exclusion experiment and continuous monitoring of the mother's social environment, allowing us to estimate how individual females adjust allocation to reproduction as their number of helpers varies. We found that egg mass varied consistently within females and did not clearly differ in relation to rainfall or predation risk. Contrary to previous studies, there was no evidence for plastic adjustments as females gained and lost helpers, and egg mass was instead better predicted by mother size and identity. Females laid larger clutches when breeding in environments where predation risk was experimentally reduced and after higher rainfall levels. Yet, there was no evidence for increasing clutch size as the number of helpers increased, nor for an interaction between helper effects and ecological factors. We conclude that while sociable weaver females can vary their clutch size, they show high individual consistency in egg mass. In addition, we found no evidence that females may maximize fitness through plastic prenatal allocation in relation to the number of helpers, or that the presence/absence of helper effects is modulated by rainfall levels or predation risk. These results challenge our current knowledge on some of the possible benefits of breeding with helpers and call for more long-term analyses on reproductive allocation adjustments in other cooperative systems.

Intermicrobial Hitchhiking: How Nonmotile Microbes Leverage Communal Motility.

Motility allows many microbes to traverse their environment to find nutrient sources or escape unfavorable environments. However, some microbes are nonmotile and are restricted to their immediate conditions. Intriguingly, sporadic reports have demonstrated that many nonmotile microbes can utilize the motility machinery of other microbes in their vicinity. This form of transportation, called hitchhiking, has been observed with both prokaryotic and eukaryotic microbes. Importantly, many hitchhiking microbes are pathogenic to humans or plants. Here, we discuss reports of intermicrobial hitchhiking to generate a comprehensive view of hitchhiking mechanisms and how such interactions may influence human and plant health. We hypothesize that microbial hitchhiking is ubiquitous in nature and may become the subject of an independent subfield of research in microbiology.

Do I Have a Personality? Endowing Care Robots with Context-Dependent Personality Traits

Recent studies have revealed the key importance of modelling personality in robots to improve interaction quality by empowering them with social-intelligence capabilities. Most research relies on verbal and non-verbal features related to personality traits that are highly context-dependent. Hence, analysing how humans behave in a given context is crucial to evaluate which of those social cues are effective. For this purpose, we designed an assistive memory game, in which participants were asked to play the game obtaining support from an introvert or extroverted helper, whether from a human or robot. In this context, we aim to (i) explore whether selective verbal and non-verbal social cues related to personality can be modelled in a robot, (ii) evaluate the efficiency of a statistical decision-making algorithm employed by the robot to provide adaptive assistance, and (iii) assess the validity of the similarity attraction principle. Specifically, we conducted two user studies. In the human–human study (N=31), we explored the effects of helper’s personality on participants’ performance and extracted distinctive verbal and non-verbal social cues from the human helper. In the human–robot study (N=24), we modelled the extracted social cues in the robot and evaluated its effectiveness on participants’ performance. Our findings showed that participants were able to distinguish between robots’ personalities, and not between the level of autonomy of the robot (Wizard-of-Oz vs fully autonomous). Finally, we found that participants achieved better performance with a robot helper that had a similar personality to them, or a human helper that had a different personality.

The Benefits of Help in Cooperative Birds: Nonexistent or Difficult to Detect?

In birds that breed cooperatively in family groups, adult offspring often delay dispersal to assist the breeding pair in raising their young. Kin selection is thought to play an important role in the evolution of this breeding system. However, evidence supporting the underlying assumption that helpers increase the reproductive success of breeders is inconsistent. In 10 out of 19 species where the effect of helpers on breeder reproductive success has been estimated while controlling for the effects of breeder and territory quality, no benefits of help were detected. Here, we use phylogenetic meta-analysis to show that the inconsistent evidence for helper benefits across species is explained by study design. After accounting for low sample sizes and the different study designs used to control for breeder and territory quality, we found that helpers consistently enhanced the reproductive success of breeders. Therefore, the assumption that helpers increase breeder reproductive success is supported by evidence across cooperatively breeding birds.

Soil Microbial Diversity Affects the Plant-Root Colonization by Arbuscular Mycorrhizal Fungi.

Terrestrial plants establish symbiosis with arbuscular mycorrhizal fungi (AMF) to exchange water and nutrients. However, the extent to which soil biodiversity influences such association remains still unclear. Here, we manipulated the soil microbial diversity using a "dilution-to-extinction" approach in a controlled pot microcosm system and quantified the root length colonization of maize plants by the AMF Rhizophagus clarus. The experiment was performed by manipulating the soil microbiome within a native and foreign soil having distinct physicochemical properties. Overall, our data revealed significant positive correlations between the soil microbial diversity and AMF colonization. Most importantly, this finding opposes the diversity-invasibility hypothesis and highlights for a potential overall helper effect of the soil biodiversity on plant-AMF symbiosis.

Hired helpers at the nest: The association between life-cycle servants and net fertility in North Orkney, 1851-1911.

The presence of kin is often, but not always, associated with higher fertility in historical populations. However, the effect of other household members on fertility is less frequently studied. While not genetically related, life-cycle servants lived and worked alongside household members and may have provided assistance to reproducing families. Female servants in particular may have helped mothers with small children through direct help with childcare activities or by replacing the economic effort of mothers whose work was not compatible with childcare. This study examines the presence of servants in the households of married women of reproductive age to assess whether households with young children are more likely to also have servants. This study uses individual-level census data from North Orkney, Scotland (1851-1911) to investigate the relationship between the presence of servants in households and a measure of recent net marital fertility, the number of women's own-children under age 5, using logistic regression models. Households with young children were more likely to have a female, but not male, servant in the household after controlling for the effects of other possible helpers, including older children, mothers, and mothers-in-law. These findings are consistent with prior research that indicates the importance of female labor to smallholder agricultural households and suggests that female servants may have provided support to reproducing families. Life-cycle servants should be considered one component of biocultural reproduction in historical Northwest Europe. The use of hired help is not restricted to contemporary or elite groups.

Co-expression of Interleukin-17A molecular adjuvant and prophylactic Helicobacter pylori genetic vaccine could cause sterile immunity in Treg suppressed mice

The increasing clinical significance of Helicobacter pylori (H. pylori) in human stomach cancer has led to global efforts to eradicate this pathogen. Recent studies have confirmed the importance of some cytokines such as Interleukin-18 (IL-18), Interleukin-8 (IL-8), Interleukin-17A (IL-17A) and Interleukin-22 (IL-22) in the pathogenesis of the so-called bacterium. This study was designed to compare the effects of Type 1T helper (Th1), Type 2T helper (Th2) cells, Regulatory T cells (Treg) and T helper 17 (Th17) modulatory effects on the efficacy of designed H. pylori vaccine by incorporating some molecular adjuvants in Treg competent and Treg suppressed groups. A bicistronic vector was used for simultaneous expression of codon-optimized Outer inflammatory protein a (OipA) gene and modified mice IL-18, IL-17A, IL-22 and Foxp3 (forkhead box P3) cytokines from four cassettes. Immunization of mice groups was performed using produced plasmids intradermally. Specific IgG1 and IgG2 and IgA antibody titers produced in mice were confirmed by enzyme-linked immunosorbent assay (ELISA) in sera and intestine obtained four weeks after the last immunization. After being stimulated with a mixture of both anti-CD28 mAb and H. pylori lysate, frequencies of single Interferon-Gamma (IFN-γ), single IL-17 and dual IFN-γ/IL-17-secreting T-cells were documented using dual-color FluoroSpot. The kinetics of Th1, Th2 and Th17 in the immunized animals was determined by relative quantification of IL-17A, IL-22, IFN-γ, IL-8, IL-2 and IL-4 specific mRNAs. Four weeks after bacterial challenge, quantitative colony count in the isolated and homogenized stomachs was utilized to assess the level of protective immunity among all groups. The results of immunologic assays showed that the highest cell-mediated immunity cytokines were produced in IL-17 receiving group in which the Treg responses were suppressed previously by the administration of the Foxp3 as an immunogen. In addition, potent clearance of Helicobacter pylori infection was seen in this group as well.

Effects of Follicular Helper T Cells and Inflammatory Cytokines on Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against the acetylcholine receptors (AChR) of the skeletal muscles. An imbalance in various T helper (Th) cells, including Th1, Th2, Th17, Th22 and follicular helper T (TFH) cells, has been found associated with immunological disturbances. In this study, we aim to investigate the role of the Th cells in peripheral blood of MG patients. A total of 33 MG patients and 34 age matched controls were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-Paque density gradient centrifugation assay. The proportion of TFH cells in PBMC were analyzed using flow-cytometry assay by determining the levels of cellular markers CD4, CXCR5, CD45RO, CD45RA and ICOS and PD-1. The levels of IFN-γ, IL-4, IL-17 and IL-21 in serum were analyzed by Cytometric Bead Array. The serum IL-22 level was analyzed by ELISA. The frequency of TFH cells in PBMCs was higher than those in healthy subjects and correlated to the severity of MG patients. The levels of pro-inflammatory cytokines IFN-γ, IL-17 and IL-21 were elevated in the serum of MG patients, while there were no significant differences regarding the levels of IL-4 and IL-22 between MG patients and control subjects. Our findings suggest that Th cells and their cytokines balance of MG patients are involved in the clinical condition or severity of MG disease.

Does Helping-at-the-Nest Help? The Case of the Acorn Woodpecker

Cooperative breeding groups often involve “helpers-at-the-nest”; indeed, such behavior typically defines this intriguing breeding system. In few cases, however, has it been demonstrated that feeding nestlings by helpers, rather than some other behavior associated with helpers’ presence, leads to greater reproductive success. One prediction of the hypothesis that feeding behavior per se is responsible for the fitness benefits conferred by helpers is that there should be close congruence between the patterns of helping-at-the-nest and the fitness effects of helpers. Here we look for such a relationship in the cooperatively breeding acorn woodpecker (Melanerpes formicivorus) in order to begin to identify the behaviors of helpers that drive the increased fitness benefits they confer. In terms of young fledged, a helper male confers approximately the same fitness benefits to a group as does a helper female; more dramatically, the effects of helper males increases with increasing food supply, most importantly the prior year’s acorn crop on which this species depends, whereas that of helper females does not. These patterns do not match the nest-feeding patterns of helpers, which are greater for females than males and do not increase with a larger acorn crop the prior autumn. In contrast, the proportion of time helpers spend tending acorn-storage facilities (granaries) and are present in or near their home territory is greater for males than females and, at least for males, positively related to the size of the acorn crop. These results fail to support the hypothesis that the primary benefit conferred by helpers is feeding young in the nest; rather, they suggest that behaviors such as territorial defense and predator detection are more important. Understanding exactly what those behaviors are in this, and most other cooperatively breeding systems, remain to be determined.