Lymphocytes In Pathogenesis Research Articles

Recent advances on the role of cytotoxic T lymphocytes in the pathogenesis of spondyloarthritis.

Spondyloarthritis (SpA) is a chronic inflammatory disorder with complex etiology and pathogenesis. Its pathogenesis likely involves a combination of different factors. These factors include host genetics, environmental triggers, and immune and microbiota dysregulation. One of the strongest genetic associations with SpA is HLA-B27, implicating the involvement of cytotoxic T lymphocytes (CTLs) in SpA pathogenesis. Despite this discovery dating back decades ago, the CTL compartment that underlies SpA inflammation has yet to be fully defined until recently. Indeed, recent published studies support a significant role that CTLs play in contributing to chronic joint inflammation, which is a hallmark of SpA pathology. In this review chapter, we discuss emerging evidence that supports a newfound role of CTLs in SpA pathogenesis. This emerging evidence includes enrichment of CTL-related genes from genome-wide association studies, overrepresentation of pathogenic synovial CTL phenotype, clonal expansion, and immune dysregulation of CTLs. The discoveries of this mounting evidence suggest that CTL homeostasis is altered, and a disrupted adaptive immunity underlies the chronic inflammatory features seen in SpA pathology.

Lymphocytes influence Leishmania major pathogenesis in a strain-dependent manner.

Cutaneous leishmaniasis (CL) is the most common form of leishmaniasis and is caused by several species of Leishmania parasite. Clinical presentation of CL varies from a self-healing infection to a chronic form of the disease determined by the virulence of infecting Leishmania species and host immune responses to the parasite. Mouse models of CL show contradictory roles of lymphocytes in pathogenesis, while acquired immune responses are responsible for host protection from diseases. To reconcile the inconclusive roles of acquired immune responses in pathogenesis, we infected mice from various genetic backgrounds with two pathogenic strains of Leishmania major, Friedlin or 5ASKH, and assessed the outcome of the infections. Our findings showed that the genetic backgrounds of L. major determine the impact of lymphocytes for pathogenesis. In the absence of lymphocytes, L. major Friedlin induced the lowest inflammatory reaction and pathology at the site of infection, while 5ASKH infection induced a strong inflammatory reaction and severe pathology. Lymphocytes ameliorated 5ASKH mediated pathology, while it exacerbated pathology during Friedlin infection. Excess inflammatory reactions, like the recruitment of macrophages, neutrophils, eosinophils and production of pro-inflammatory cytokines, together with uncontrolled parasite growth in the absence of lymphocytes during 5ASKH infection may induce severe pathology development. Taken together our study provides insight into the impact of differences in the genetic background of Leishmania on CL pathogenesis.

The Role of Innate and Adaptive Immune Response Lymphocytes in Pathogenesis of Hemorrhagic Fever with Renal Syndrome

The Role of Innate and Adaptive Immune Response Lymphocytes in Pathogenesis of Hemorrhagic Fever with Renal Syndrome

Interactions between dendritic cells and T lymphocytes in pathogenesis of nasal polyps.

The aim of the present study was to investigate the functional status of dendritic cells (DCs) in nasal polyps (NP) and their interactions with T lymphocytes. The interactions between DC and T lymphocytes in the pathogenesis of NP was also studied. The expression of cluster of differentiation (CD)1a and CD83 in NP was detected using immunohistochemistry and the ratio of CD83 DC/CD1a+DC was counted. The distribution of DCs in NP and normal inferior turbinate mucosa (nITM) was evaluated using double immunostaining (CD1a/CD40) and low illumination fluorescence microscopy. The number of CD1a+ cells, CD83+ cells and CD1a/CD40-dual positive cells in was significantly higher in NP tissues compared with nITM. Furthermore, the density of DCs observed in NP was significantly greater than that observed in nITM. The ratio of CD83 DC/CD1a+DC in NP was significantly higher compared with in nITM tissues. The results of the present study revealed significant infiltration of DCs in NP, with the majority being mature DCs. DCs are able to interact with T cells via the CD40/CD40L costimulatory factor, thus serving an important role in the development and progression of NP.

Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases

Autoimmune thyroid disorders (AITD) broadly include Graves’ disease and Hashimoto’s thyroiditis which are the most common causes of thyroid gland dysfunctions. These disorders develop due to complex interactions between environmental and genetic factors and are characterized by reactivity to self-thyroid antigens due to autoreactive lymphocytes escaping tolerance. Both cell-mediated and humoral responses lead to tissue injury in autoimmune thyroid disease. The differentiation of CD4+ cells in the specific setting of immune mediators (for example cytokines, chemokines) results in differentiation of various T cell subsets. T cell identification has shown a mixed pattern of cytokine production indicating that both subtypes of T helper, Th1 and Th2, responses are involved in all types of AITD. Furthermore, recent studies described T cell subtypes Th17 and Treg which also play an essential role in pathogenesis of AITD. This review will focus on the role of the T regulatory (Treg) and T helper (Th) (especially Th17) lymphocytes, and also of B lymphocytes in AITD pathogenesis. However, we have much more to learn about cellular mechanisms and interactions in AITD before we can develop complete understanding of AITD pathophysiology.

Research progress of Blimp-1 regulating T lymphocytes in pathogenesis of aplastic anemia

Aplastic anemia (AA) is considered as an immune-mediated bone marrow failure, but the specific pathogenesis is still under-researched. B lymphocyte-induced maturation protein (Blimp)-1 is a transcriptional repressor encoded by positive regulatory domain (PRDM)1 gene and is required to trigger the maturation of B lymphocytes into antibody secreting cells. Mounting evidence suggests that Blimp-1 plays a common role in the terminal differentiation of multiple T lymphocyte subsets, and functions significantly in the pathogenesis of many immune disorders. Here, we summarized the function of T lymphocytes in AA and the recent advances on the relationships of Blimp-1 and T lymphocytes, and we discuss the role of Blimp-1 regulating T lymphocytes in pathogenesis of AA. Key words: Blimp-1; T-lymphocytes; Anemia, aplastic; B lymphocyte-induced maturation protein-1

Value Research of T-Regs Cells in Peripheral Blood of Patients with Multiple Myeloma

In this study we have assessed FOXP3 and its isoforms expression by CD4+ T cells from peripheral blood of 37 patients with various forms of multiple myeloma (MM) and 15 healthy volunteers. Newly diagnosed MM was in 17 patients; resistant/relapsed MM was registered in 13 patients and 7 patients had remission after chemotherapy. Significant role of FOXP3 expression by CD4+ T lymphocytes in pathogenesis of MM was shown. Thus, increase of FOXP3-expressing cells percent among CD4+ T cells is registered in patients with newly diagnosed MM and in resistant/relapsed patients. The main contribution to this percent increment is made by FOXP3D2 isoform expressing cells. In addition to the percent increment the number of CD4+FOXP3+ T cells is also risen in patients with newly diagnosed MM. The level of FOXP3 expression by CD4+ T cells also reflects the effectiveness of antitumor therapy, considering normalization of CD4+FOXP3+ T cells number and percent in patients with disease remission. We also discuss the possible relationship between FOXP3 mRNA post-transcriptional modification, namely alternative splicing, with stable expression of FOXP3 in T-regs cells.The level of an expression of T-regs cells can will be applied as criterion of efficiency of antitumor therapy. DisclosuresNo relevant conflicts of interest to declare.

The role of Th17 lymphocytes in pathogenesis of autoimmune arthritides

Abstract Th17 cells are newly described population of lymphoctyes, that recruits neutrophils to the site of inflammation and activate inflammatory phenotype of various tissues. They also play a pivotal role in autoimmune diseases and cancers. These cells secrete mainly different isoforms of IL-17, but also IL-21 and IL-22. Rheumatoid arthritis and juvenile idiopathic arthritis are the most common autoimmune joints’ inflammatory disease, affecting respectively adults and children. For a long time the immunopathogenesis of autoimmune diseases has been associated with Th1 lymphocytes. This hypothesis has changed after the discovery of Th17 cells, which are thought to be key mediators of autoimmune arthritides

Role of Th17 lymphocytes in pathogenesis of colorectal cancer

Colorectal cancer (CRC) is estimated to be the first leading cause of death from cancer among men and women in the EU. Every year in Poland, 15,254 cases of CRC are diagnosed, and 10,501 patients die of the disease, making it the second leading cause of death from cancer. In more than 90% of cases, the disease begins as adenomatous polyps with epithelial dysplasia as a common feature. Inflammatory bowel diseases (IBD), a group of chronic inflammatory diseases of the gastrointestinal tract characterized by remissions and relapses, constitute an independent risk factor of CRC development. CRC developing in IBD patients, however, has features distinct from sporadic cancer, suggesting the influence of unique factors. The high risk of CRC in IBD patients probably results from chronic inflammation. In most cases, neoplastic lesions arise within the inflamed gastrointestinal mucosa during the process of re-epithelization, which is a healing response to ulceration. The recently discovered Th17 lymphocytes, which demonstrate strong pro-inflammatory capabilities, might link the two diseases. Th17 lymphocytes produce a number of pro-inflammatory cytokines, such as interleukin (IL)-17A, IL-17F, IL-21, IL-22 and tumor necrosis factor (TNF)-a, and play a key role in mucosal defense against various pathogens. Numerous observations suggest that Th17 lymphocytes are involved in pathogenesis of different autoimmune diseases and pathologic inflammatory states. Mounting evidence suggests that Th17 cells contribute to the pathogenesis of IBD and CRC. However, their precise role in both diseases is unknown.

Distribution of γδ and other T-lymphocyte subsets in patients with chronic obstructive pulmonary disease and asthma

The role of T lymphocytes in pathogenesis of chronic inflammatory airway diseases - asthma and chronic obstructive pulmonary disease (COPD) has been emphasized in recent years: the importance of αβ T-cells (CD8+ and CD4+) has been widely described. A substantial fraction of γδ T-cells is a composite part of pulmonary T lymphocytes. Specific localisation of γδ T-cells in epithelium/mucosa-rich tissues implies their potential role in local inflammatory immune response, which occurs in chronic inflammatory airway diseases. An investigation was made of the T-lymphocyte subsets in induced sputum (IS), in bronchoalveolar lavage (BAL) and in peripheral blood from 20 patients with COPD (stages II-III; GOLD), 18 patients with asthma (persistent mild to moderate; GINA) and 14 healthy subjects. Relationship of γδ T-cells with lung function and smoking history was analysed. COPD patients had significantly higher numbers of CD8+T-cells in the airways of smokers compared to ex-smokers in the COPD group. A significant positive correlation was found between CD8+T-cells and pack-years of smoking. Differently, the COPD patients had significantly lower relative and absolute numbers of γδ T-cells in IS and in BAL compared to those from asthma or healthy subjects. The quantity of γδ T-cells negatively correlated with forced expiratory volume in 1s and smoking (pack-years) only in COPD group. Our findings indicate a different local inflammatory response in COPD patients and in asthmatic groups. The reduced amount of γδ T-cells in IS and in BAL from COPD patients raises the hypothesis about their important role in pathogenesis of COPD.

CCR2-dependent intraepithelial lymphocytes mediate inflammatory gut pathology during Toxoplasma gondii infection

Mice of the C57BL/6 strain develop acute ileal inflammation after infection with the protozoan parasite Toxoplasma gondii. This pathology resembles many key features of human Crohn's disease, including a Th1 cytokine profile with high levels of interferon γ (IFN-γ), interleukin 12 (IL)-12, and tumor necrosis factor α (TNF)-α, presence of pathogenic CD4+ T cells, and infiltration of gut flora into inflammed tissue. Using CCR2−/− mice, we identify a role for this chemokine receptor in the pathogenesis of inflammatory pathology during T. gondii infection. Lack of chemokine (C–C motif) receptor 2 (CCR2) was associated with low levels of CD103+ T lymphocytes in the intraepithelial compartment, Peyer's patch, and lamina propria relative to wild-type animals. Adoptive transfer of wild-type, but not IFN-γ−/−, intraepithelial T lymphocytes converted CCR2 knockout mice from a resistant to susceptible phenotype with respect to parasite-triggered inflammatory gut pathology. These results for the first time show a role for intraepithelial T lymphocytes in pathogenesis of ileitis triggered by a microbial pathogen.

Increased serum levels of neopterin and soluble interleukin-2 receptor in intrahepatic cholestasis of pregnancy.

The etiology of intrahepatic cholestasis of pregnancy (ICP), a pregnancy-specific complication, remains not completely understood. Some alterations of immunity in ICP were reported, but the profile of immune alteration was far from clarified. The aim of this investigation was to characterize the changes of serum levels of neopterin, a marker for the activation of macrophage, and soluble interleukin-2 receptor (sIL-2R), a marker for the activation of lymphocyte, in ICP. Serum levels of neopterin and sIL-2R were assayed with enzyme linked immunosorbent assay (ELISA) in 30 patients with ICP and 30 normal pregnant women. Student's t-test was used for statistic analysis, and p < 0.05 was considered significant. Compared with control, serum levels of neopterin (p < 0.005) and sIL-2R (p < 0.05) were increased significantly in women with ICP. Activation of monocyte-macrophage and lymphocyte was demonstrated in ICP, and the participation of the activation of macrophage and lymphocyte in pathogenesis of the disease could be assumed.

Increased serum levels of neopterin and soluble interleukin-2 receptor in intrahepatic cholestasis of pregnancy

Objectives. The etiology of intrahepatic cholestasis of pregnancy (ICP), a pregnancy-specific complication, remains not completely understood. Some alterations of immunity in ICP were reported, but the profile of immune alteration was far from clarified. The aim of this investigation was to characterize the changes of serum levels of neopterin, a marker for the activation of macrophage, and soluble interleukin-2 receptor (sIL-2R), a marker for the activation of lymphocyte, in ICP. Methods. Serum levels of neopterin and sIL-2R were assayed with enzyme linked immunosorbent assay (ELISA) in 30 patients with ICP and 30 normal pregnant women. Student's t-test was used for statistic analysis, and p < 0.05 was considered significant. Results. Compared with control, serum levels of neopterin (p < 0.005) and sIL-2R (p < 0.05) were increased significantly in women with ICP. Conclusions. Activation of monocyte-macrophage and lymphocyte was demonstrated in ICP, and the participation of the activation of macrophage and lymphocyte in pathogenesis of the disease could be assumed.

Breaking the rules: the unconventional recognition of HLA-B27 by CD4+ T lymphocytes as an insight into the pathogenesis of the spondyloarthropathies.

Despite extensive research, it remains unclear why a small proportion of HLA- B27(+) individuals develop spondyloarthropathies (SpA). Because the function of HLA-B27, as a major histocompatibility complex (MHC) class I molecule, is peptide presentation to CD8(+) T cells, research has concentrated on the role of HLA-B27 as a restriction element for CD8(+) cytotoxic T lymphocytes in pathogenesis. However, findings in the B27-transgenic animal models, together with the identification of unusual processing and presentation features of HLA-B27, have raised alternative hypotheses for the pathogenic role of HLA-B27. One such hypothesis is that HLA-B27 can be recognized by CD4(+) T lymphocytes. Here we report the identification of such unusual cells, which break the conventional rules of MHC restriction, and propose a model for the role of such CD4(+) T cells in SpA.

Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice

The aims of the study were to compare the pathogenesis of Candida albicans infection in various organs and anatomical regions of C5-deficient (DBA/2) and C5-sufficient (BALB/c) mice, and to evaluate the importance of complement C5 and T lymphocytes as factors that determine host susceptibility or resistance. The kidneys of DBA/2 mice showed higher colonisation and more severe tissue damage than those of BALB/c, but infection at other sites, including oral and vaginal mucosa, was generally similar in the two strains. Passive transfer of C5-sufficient serum into DBA/2 mice decreased the fungal burden in the kidney, and prolonged survival of the reconstituted animals. Depletion of CD4 + and/or CD8 + cells did not exacerbate either systemic or mucosal infection when compared to controls, and passive transfer of splenocytes from infected donors caused only a small and transient reduction in numbers of yeasts recovered from the kidney of sub-lethally infected recipients. It is concluded that the acute susceptibility of the kidneys in this mouse strain is due to C5 deficiency expressed on a susceptible genetic background. T lymphocytes, however, appear to have minimal influence on recovery from systemic infection with this isolate of C. albicans.

Synergism between Adriamycin and Coxsackie Virus Group B Type 3 (CVB3) in Induction of Myocardial Injury: Potential Role for γ/δ TcR + T Lymphocytes in Pathogenesis

Synergism between Adriamycin and Coxsackie Virus Group B Type 3 (CVB3) in Induction of Myocardial Injury: Potential Role for γ/δ TcR + T Lymphocytes in Pathogenesis