T-cellular Immunity Research Articles

Persistence of T-Cell Immunity Responses against SARS-CoV-2 for over 12 Months Post COVID-19 Infection in Unvaccinated Individuals with No Detectable IgG Antibodies.

Immune response to SARS-CoV-2 is crucial for preventing reinfection or reducing disease severity. T-cells' long-term protection, elicited either by COVID-19 vaccines or natural infection, has been extensively studied thus far; however, it is still attracting considerable scientific interest. The aim of the present epidemiological study was to define the levels of T-cellular immunity response in a specific group of unvaccinated individuals from the general population with a prior confirmed COVID-19 infection and no measurable levels of IgG antibodies. We performed a retrospective descriptive analysis of data collected from the medical records of consecutive unvaccinated individuals recovered from COVID-19, who had proceeded to a large private medical center in the Attica region from September 2021 to September 2022 in order to be examined on their own initiative for SARS-CoV-2 T-cell immunity response. The analysis of T-cell responses was divided into three time periods post infection: Group A: up to 6 months; Group B: 6-12 months; Group C: >12 months. The SARS-CoV-2 T-cell response was estimated against spike (S) and nucleocapsid (N) structural proteins by performing the T-SPOT. COVID test methodology. SARS-CoV-2 IgG antibody levels were measured by the SARS-CoV-2 IgG II Quant assay (Abbott Diagnostics). A total of 182 subjects were retrospectively included in the study, 85 females (46.7%) and 97 (53.3%) males, ranging from 19 to 91 years old (mean 50.84 ± 17.2 years). Among them, 59 (32.4%) had been infected within the previous 6 months from the examination date (Group A), 69 (37.9%) had been infected within a time period > 6 months and <1 year (Group B) and 54 (29.7%) had been infected within a time period longer than 1 year from the examination date (Group C). Among the three groups, a positive T-cell reaction against the S antigen was reported in 47/58 (81%) of Group A, 61/69 (88.4%) of Group B and 40/54 (74.1%) of Group C (chi square, p = 0.27). T-cell reaction against the N antigen was present in 45/58 (77.6%) of Group A, 61/69 (88.4%) of Group B and 36/54 (66.7%) of Group C (chi square, p = 0.02). The median Spot-Forming Cells (SFC) count for the S antigen was 18 (range from 0-160) in Group A, 19 (range from 0-130) in Group B and 17 (range from 0-160) in Group C (Kruskal-Wallis test, p = 0.11; pairwise comparisons: groups A-B, p = 0.95; groups A-C, p = 0.89; groups B-C, p = 0.11). The median SFCs count for the N antigen was 14.5 (ranging from 0 to 116) for Group A, 24 (ranging from 0-168) in Group B and 16 (ranging from 0-112) for Group C (Kruskal-Wallis test, p = 0.01; pairwise comparisons: groups A-B, p = 0.02; groups A-C, p = 0.97; groups B-C, p = 0.03). Our data suggest that protective adaptive T-cellular immunity following natural infection by SARS-CoV-2 may persist for over 12 months, despite the undetectable humoral element.

Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.

BackgroundDialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality.MethodsWe conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273.ResultsSARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%). T-cellular immunity largely mimicked humoral results. Major risk factors of seroconversion failure were immunosuppressive drug number and type (belatacept, MMF-MPA, calcineurin-inhibitors) as well as vaccine type (BNT162b2 mRNA). Seroconversion rates induced by mRNA-1273 compared to BNT162b2 vaccine were 97% to 88% (p < 0.001) in dialysis and 49% to 26% in transplant patients, respectively. Specific IgG directed against the new binding domain of the spike protein (RDB) were significantly higher in dialysis patients vaccinated by mRNA-1273 (95%) compared to BNT162b2 (85%, p < 0.001). Vaccination appeared safe and highly effective demonstrating an almost complete lack of symptomatic COVID-19 disease after boost vaccination as well as ceased disease incidences during third pandemic wave in dialysis patients.ConclusionDialysis patients exhibit a remarkably high seroconversion rate of 95% after boost vaccination, while humoral response is impaired in the majority of transplant recipients. Immunosuppressive drug number and type as well as vaccine type (BNT162b2) are major determinants of seroconversion failure in both dialysis and transplant patients suggesting immune monitoring and adaption of vaccination protocols.

Vaccination with Live Attenuated Virus Vaccines in Four Pediatric Patients with CML While on Imatinib Treatment

Background: Documented experience on vaccination while on imatinib treatment is missing in children. According to current recommendations for all age groups of immunocompromised individuals inactive vaccines can safely be administered. However, depending on the grade of immunosuppression the immune response may be reduced or missing. Live attenuated vaccines must not be administered to immunosuppressed individuals according to general recommendations. To date, very few in vivo human studies have addressed the long-term impact of imatinib on the immune function. Data from in vitro and animal studies have documented seemingly contradictory effects of imatinib, ranging from impaired antigen-specific T-cell responses to reversal of T-cell tolerance and potentiation of antitumor immune responses. In adult patients (pts) with CML treated with imatinib, the B-cell response to inactivated vaccines against pneumococcus as well as H1N1 influenza virus was impaired and associated with loss of memory B-cell subsets [de Lavallade H, et al. Haematologica 2011; Blood 2013]. Accordingly, several adult cases of reactivation of hepatitis B virus infection under imatinib have been observed [Mallet V, et al. Lancet Infect Dis. 2016]. On the other hand, no opportunistic infections or uncommon courses of an infection were observed in the so far largest pediatric CML trial while pts were on imatinib treatment [Suttorp M, et al. Leukemia 2018]. The growing anti-vaccination movement in many countries based heavily on non-rational objections to vaccinations poses a world-wide threat to public health. In Europe, the number of reported cases of measles in 2018 was triple that in 2017 and 15 times that in 2016 (Thornton J, Br Med J 2019). To what extend this scenario poses any extra risk on CML pts is completely unknown. Methods: Four pediatric pts (10, 11, 12, 14 yrs old) with complete or partially non-protective titers against measles, mumps, rubella, and/or varicella were vaccinated after informed consent following individual assessments of risk and benefits once stable remission of CML had been achieved. Commercially available vaccines (M-M-RVAX Pro®, Varivax®, Priorix-Tetra®) were administered at lymphocyte counts &gt;1500/µl. Details are listed in the table. Pt #4 was vaccinated 1 week after interruption of imatinib treatment followed by a 2 week cessation while the other 3 pts were vaccinated under ongoing imatinib treatment. Results: All seven live virus vaccinations in the 4 pts were well tolerated and no acute or late adverse events were observed (see table). Seroconversion could be confirmed in pts #1 and #3, while in pt #2 the first vaccination against measles, mumps, and rubella performed 11 months after diagnosis of CML was unsuccessful. However, revaccination three years later resulted in seroconversion. Interestingly, vaccination of this girl against varicella in the 54th month of imatinib treatment resulted in no measurable VZ-IgG in serum. Pt #4 lost his protective measles titer 7 months after vaccination when the imatinib dose was weight-adapted and increased but responded with protective titers to revaccination. Discussion: As a word of caution no sound conclusions can be drawn from this small series of only 7 vaccinations in 4 pts. Noteworthy, no adverse events resulting from attenuated live viral vaccines were observed in this cohort. The initial non-response in pt #2 when vaccinated 11 months after diagnosis of CML cannot be explained. A missing detection of varicella zoster IgG is observed in 1-5 % of healthy vaccinees and is caused by acquired T-cellular immunity against varicella (not investigated in this case). An alternative approach to be explored for administering live virus vaccination is short interruptions of imatinib treatment (2-3 weeks "off" the drug once molecular remission is achieved, pt #4). As long as herd immunity against dangerous diseases like measles is not established in many countries, pts with CML require protection. In order to accumulate knowledge we suggest that any experience with live virus vaccines in children with CML should be documented in an international registry. Disclosures No relevant conflicts of interest to declare.

FEATURES OF THE SITUATION OF THE IMMUNE SYSTEM IN WOMEN WITH UTERINE LEIOMYOMA AFTER EMBOLIZATION OF UTERINE ARTERIES

One of the most effective treatment for uterine leiomyomas is uterine artery embolization. However, its impact on the immune system of women is still insufficiently studied.The aim of the study- to investigate the state of non-specific and specific cells of cellular immunity in women with uterine leiomyoma after embolization of uterine arteries, depending on the peculiarities of the post-embolisation period.Material and methods of research - For the purpose of conducting immunological studies, whole peripheral blood and its serum of women with leiomyoma of the uterus were used before and after the embolization of the uterine arteries.The article presents: Evaluation of nonspecific and specific components of cellular immunity in women with uterine leiomyoma one month after the uterine arteries embolization did not reveal any significant changes compared with the indicators before it was performed. It may attest the safety of this intervention. However women with inflammatory complications after UAE usually have abnormal function of phagocytes and T-cellular immunity, as well as the level of circulating immune complexes, mainly due to low molecular weight subunits, which have a damaging effect on the endothelium of the vessels.Conclusion. On the basis of the obtained data, it can be argued that patients with uterine leiomyoma who are planning to embryo uterine arteries are advised to carry out the prevention of inflammatory complications after intervention in order to reduce the likelihood of changes in the immune system.

FEATURES OF THE IMMUNOLOGICAL STATUS IN PATIENTS WITH DIFFERENT FORMS OF TRANSIENT DISTURBANCES OF CEREBRAL BLOOD CIRCULATION

Objective : to determine special features of the immunological status as a result of immunophenotyping of peripheral blood leukocytes in patients with different transient disturbances of cerebral blood circulation in comparison with patients with stroke. Material and methods . We examined 14 patients with transient ischemic attack (TIA), 7 patients with cerebral hypertensive crisis (CHC), 9 patients with lacunar stroke, and 9 volunteers. All the patients underwent immunophenotyping of peripheral blood leukocytes and their immunoglobulin level was determined by immunoturbodimetrical method on the first day after admission. Results . We have defined the specific features of the inflammatory process presented by activation of the classical way of inflammation in CHC patients on the first day of the illness in the form of increased level of proteins of the complement system, activity of T- and B-cellular links of immunity in a combination with low expression of adhesion molecules. We have revealed depression of T-cellular immunity without activation of B-cellular immunity in TIA group, which distinguishes transient disturbances of cerebral blood circulation from stroke. Conclusion. Absence of the activation of B-cellular immunity in patients with CHC and TIA and low level of the expression of adhesion molecules make the sanogenic potential of transient disturbances of cerebral blood circulation in comparison with stroke.

Psychoimmune Interactions in Women of Reproductive Age with Endometriosis

Psychoimmune interactions were studied in women of reproductive age with endometriosis. Pronounced immunological shifts manifested in a shift of the T-cellular immunity, resulting in imbalanced production of pro- (IL-1β, IL-2, IFN-γ) and anti-inflammatory (IL-4) cytokines. Significant correlations between the severity of mental shifts and immunopathogenetic factors in the studied patient population demonstrated the psychoneuroimmune nature of endometriosis.

Responses of thymocytes and splenocytes to low-intensity extremely high-frequency electromagnetic radiation in normal mice and in mice with systemic inflammation

Changes in T cell subsets and expression of cytokine genes in thymocytes and splenocytes after exposure of BAL/c mice to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, exposure duration 20 min) under normal conditions and in systemic inflammation were studied using flow cytometry and the methods of reverse transcription and real-time polymerase chain reaction. It was found that the number of CD4+ and CD8+ T cells statistically significantly increased in the thymus and considerably decreased in the spleen of exposed animals. Apparently, the exposure of animals leads to an intensification of the host defense, by activating the T-cellular immunity. As for effector functions, the increased expression of IL-1beta and IFNgamma genes in thymocytes and essentially enhanced expression of IL-1beta, IL-10, and TNFalpha genes in splenocytes were observed in mice exposed against the background of a progressive inflammatory process. The experimental data obtained specify that the directed (anti-inflammatory) response of an organism to a specific combination of effective exposure parameters of electromagnetic radiation can be realized by the activation of particular immunocompetent cells and changes in the cytokine profile.

Designing Short Peptides as Viral Vaccines

The genetic diversity across global population (Black, Caucasoid, oriental, Hispanic, mixed race, Pacific Islander, American Indian and Australian aboriginal) are other vital issues in personalized/population based medicine. The human leukocyte antigen (HLA) genes in human chromosome 6 are extensively studied across global population using genetic data and about a 2000 HLA alleles have been named so far at IMGT/HLA database. Extensive HLA polymorphism and peptide diversity are critical issues in HLA-peptide binding estimation for T-cell mediated immune response. The precise evaluation of HLA peptide binding finds application in epitope design for the development of vaccines and diagnostics of diseases associated with CD4+ (example, type 1 diabetes, malaria) and CD8+ (example, several viral infections) T-cellular immunity. HLA class II binding peptides have an extended conformation at the binding groove unlike class I. This increases peptide binding combinations of varying length at the groove having eventual effect in the host immune response to infectious agents. Discussion on the significance of prediction models to large HLA allele coverage representing sampled global population towards the development of diagnostics and vaccines will be presented.

Class II HLA-peptide binding prediction using structural principles

The precise prediction of class II human leukocyte antigen (HLA) peptide binding finds application in epitope design for the development of vaccines and diagnostics of diseases associated with CD4+ T-cellular immunity. HLA II binding peptides have an extended conformation at the binding groove unlike class I. This increases peptide binding combinations of varying length at the groove, having an eventual effect in the host immune response to infectious agents. Here we describe the development of a prediction model using information gleaned from HLA II-peptide (HLA II-p) structural data. We created a manually curated dataset of 15 HLA II-p structural complexes from Protein databank (PDB). The dataset was used to develop virtual binding pockets for accommodating HLA-II–specific short peptides. The binding of peptides to the virtual pockets is estimated using the Q matrix (a quantitative matrix based on amino acid residue properties). Internal cross-validation of the model using the 15 HLA II-p structural complexes produced an accuracy of 53% with a sensitivity of 53%. The model was further evaluated using a dataset of 3676 class II–specific peptides consisting of 1188 binders and 2488 nonbinders derived from MHCBN (a database of HLA binders and nonbinders). The model produced an accuracy of 53% with 70.8% specificity and 27.6% sensitivity. The positive predictive value (PPV) was 62% and the negative predictive value (NPV) 58%. A 62% PPV suggests that the model fairly predicts a good number of binders among predicted binders and thus that the success rate among predicted binder for further verification is good. The described model is simple and rapid, with large HLA allele coverage representing the sampled global population, despite weak prediction accuracy. The ability of the model to predict a wide array of defined class II alleles is found to be applicable for proteome-wide scanning of parasitic genomes.

Hepatitis C Virus Infection Induced Vasculitis

Cryoglobulinemia are immune complexes that may induce systemic cryoglobulinemic vasculitis, a small-vessel vasculitis involving the skin, the joints, the peripheral nerve system, and the kidneys. During the last 15 years, progresses have been done after the discovery of the hepatitis C virus, the main cause of cryoglobulins. Main factors associated with cryoglobulin production are female gender, alcohol intake above 50 g/day, extensive liver fibrosis, and steatosis. Symptomatic cryoglobulins (i.e., vasculitis) are associated with older age, longer duration of infection, and main characteristics of cryoglobulin (type II, IgM kappa, high serum levels). The physiopathology is complex, and it involves humoral immunity, B- and T-cellular immunity but not the virus itself. Peg-Interféron alpha Ribavirine combination leads to a virological and clinical response of the vasculitis in about 70% of patients. In nonresponders, recent open series suggested the efficacy of Rituximab with a good response in up to 80% of patients but a relapse in 42% after 7 months after the last infusion. For future prospects and projects, new therapeutic strategies include a combination of best antiviral treatment with Peg-Interferon plus Ribavirin and Rituximab. Multicenter controlled trials are mandatory.

Age related changes in population of peripheral T cells: towards a model of immunosenescence

In this paper, we presented the results of analysis of experimental evidence for the decline of the human immune system functioning with age using mathematical model of immunosenescence. The most prominent changes in this system are related to the decline in the T-cellular immunity. These include the decline in the naı̈ve T cells generation rate, shrinkage of the volume of the peripheral lymphoid tissue, decline of absolute and relative concentrations of naı̈ve T cells in the blood, shortening of the average telomere length of T cells. These alterations in the immune system are responsible for sharp increase of morbidity and mortality caused by infectious agents at old ages. Analysis shows that concentrations of memory and naı̈ve T cells in peripheral lymphoid tissue are the key variables in this process. Simulation experiments with our model show that the average life span of memory T cells must grow with age, and that decreasing of antigenic load led to considerable increase in organism's resistance in middle ages, but only to slight increase in old ages. Restriction in the rate of thymus involution resulted in an increase of organism's resistance to infections in old ages. However, this growth is accompanied by the decline of concentration of memory T cells and shortening of their life span. The proposed model describes the trade-off between concentrations of naı̈ve and memory T cells and their potential to proliferate in human organism.

Dehydroepiandrosterone decreases mortality rate and improves cellular immune function during polymicrobial sepsis.

Sepsis is associated with a marked depression of cellular immune function. The steroid hormone dehydroepiandrosterone (DHEA) is proposed to have immunoenhancing activities. We, therefore, investigated the effect of DHEA on the mortality rate and cellular immune functions in an experimental model of sepsis. Randomized animal study. Level I trauma center, university research laboratory. Male NMRI mice. Mice were subjected to laparotomy (sham) or cecal ligation and puncture (CLP). Mice were treated with (sham/DHEA; CLP/DHEA) or without (sham; CLP) the steroid hormone DHEA (30 mg/kg sc). Animals were killed 48 hrs after the onset of sepsis. The survival rate of septic mice was determined 24 and 48 hrs after onset of sepsis. Forty-eight hours after the septic challenge, a white blood cell count was performed and serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta concentrations were monitored using ELISA. Furthermore, the delayed type of hypersensitivity (DTH) reaction was evaluated on the basis of ear pinna swelling after dinitrofluorobenzene (DNFB) administration, and clinical variables (body weight, temperature, heart rate, fluid input/output, food intake) were monitored using metabolic cages. DHEA administration improved the survival rate (87% vs. 53% after 48 hrs; p <.001). This was accompanied by a restoration of the depressed DTH reaction and a reduction in TNF-alpha serum concentrations (20.7 +/- 1.4 pg/mL vs. 32.4 +/- 6.6 pg/mL). These results demonstrate that DHEA administration leads to an increased survival following a septic challenge. The immunoenhancing effect of DHEA is accompanied by a reduction of TNF-alpha release and an improved activity of T-cellular immunity. DHEA administration may, therefore, be beneficial in systemic inflammation.

Stress-induced suppression of the cellular immune reactions: On the neuroendocrine control of the immune system

Immune competence is considered as a state of equilibrium between humoral and cellular immunity. This notion fits well with the functionally antagonistic cytokine profiles in cell groups of CD4 +-helper cells as described by Mosmann and Coffman. The Th-1 cells release mainly IL-2, IL-12 and IFNγ and thereby stimulate the cellular immune reactions. Conversely, the Th-2 cells produce predominantly IL-4, IL-6 and IL-10, thus enhancing humoral immune reactions. Recently, it has been shown that the lymphokine profiles in Th-2 are linked to changes of the humoral balance between cortisol and dehydroepiandrosterone. These studies show that there exist states of equilibrium between T- and B-cell-mediated immune reactions, which may selectively be altered to the disadvantage of the T-cellular immunity by a stress-induced enhancement of cortisol release. In an attempt to restitute stress-induced immunosuppression, a dampening of the cortisol release hormone in the hypothalamus should, therefore, be of primary importance.

Effects of plasmapheresis and immunocorrecting therapy on T-immunity of pa¬tients with autoimmune thyroiditis

T-cellular immunity was studied in 104 patients with autoimmune thyroiditis to assess the function of the thyroid and treatment method. A reliable reduction of the activity of T-lymphocyte receptor system, lymphopoiesis activation, and their relationship with the thyroid status were revealed. Plasmapheresis as monotherapy was used in 22 patients. It brought about a short-term positive effect, this necessitating search for other methods of' immunorehabilitation. In 82 patients it was supplemented with immunocorrecting therapy (thymalin) and in 49 with hypothyrosis with substitution therapy (L-thyroxine, thyroidin). Combined therapy helped attain a stable clinical and immunological effect. Subpopulation composition of T-lymphocytes recovered, their functional activity normalized (follow-up period 1 year).

Parathyroid hormone and T-cellular immunity in uremic patients in replacement dialytic therapy.

We studied 54 patients in replacement dialytic therapy divided into two groups: Group 1, 26 patients with normal parathyroid hormone (PTH) (10-80 pg/ml): and Group 2, 28 patients with elevated PTH (80-400 pg/ml). Total T lymphocytes, CD4, CD8, and CD4/CD8 ratio were evaluated. We found a reduction of total T lymphocytes in both groups compared with controls. A decrease of CD4 and CD4/CD8 ratio with a rise of CD8 occurred in Group 2 but not in Group 1. In Group 2, PTH presented a linear correlation with CD8 and a reverse correlation with total T cells. CD4, and CD4/CD8 ratio. PTH might act on T-cellular immunity with an immunosuppressive effect from the earlier phases of hyperparathyroidism.