Gamma delta T cells in non‐immune patients during primary schistosomal infection

Schwartz, Eli; Rosenthal, Etti; Bank, Ilan

doi:10.1002/iid3.18

Cited by 6 publications

(8 citation statements)

References 32 publications

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“…One strength of our study is that we did not limit our analysis to CD4 T cells, which allowed us to detect a strong γδ T cell response to SWAP antigen. γδ T cells are elevated in the blood of individuals with acute schistosomiasis, however this analysis was not done in an antigen-specific fashion [ 25 ]. Here we provide evidence that γδ T cells respond to SM in an antigen specific manner in that they are activated by SWAP but not by SEA.…”

Section: Discussionmentioning

confidence: 99%

“…They canonically proliferate and produce IFNγ in response to phosphoantigens produced by pathogens [ 22 , 23 ]. Vγ2Vδ2 T cell populations expand in the peripheral blood of people in response to a variety of infections [ 22 , 24 ] including SM [ 25 ]. While it is clear that γδ T cells respond to infection with helminths, whether they respond to helminth antigen directly or are merely bystander cells is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis

et al. 2020

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Schistosoma mansoni (SM) is a parasitic helminth that infects over 200 million people and causes severe morbidity. It undergoes a multi-stage life cycle in human hosts and as such stimulates a stage-specific immune response. The human T cell response to SM is complex and varies throughout the life cycle of SM. Relative to the wealth of information regarding the immune response to SM eggs, little is known about the immune response to the adult worm. In addition, while a great deal of research has uncovered mechanisms by which coinfection with helminths modulates immunity to other pathogens, there is a paucity of data on the effect of pathogens on immunity to helminths. As such, we sought to characterize the breadth of the T cell response to SM and determine whether co-infection with Mycobacterium tuberculosis (Mtb) modifies SM-specific T cell responses in a cohort of HIV-uninfected adults in Kisumu, Kenya. SM-infected individuals were categorized into three groups by Mtb infection status: active TB (TB), Interferon-γ Release Assay positive (IGRA+), and Interferon-γ Release Assay negative (IGRA-). U.S. adults that were seronegative for SM antibodies served as naïve controls. We utilized flow cytometry to characterize the T cell repertoire to SM egg and worm antigens. We found that T cells had significantly higher proliferation and cytokine production in response to worm antigen than to egg antigen. The T cell response to SM was dominated by γδ T cells that produced TNFα and IFNγ. Furthermore, we found that in individuals infected with Mtb, γδ T cells proliferated less in response to SM worm antigens and had higher IL-4 production compared to naïve controls. Together these data demonstrate that γδ T cells respond robustly to SM worm antigens and that Mtb infection modifies the γδ T cell response to SM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis

et al. 2020

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“…During schistosomiasis, the response to schistosome antigen is primarily mediated by activated CD4 + αβ T cells (33). However, it has also been reported that γδ T cells are recruited to egg-induced granuloma in the murine schistosomiasis (124) and that the levels of γδ T cells are increased in schitosome-infected mice and patients (125,126). However, an earlier study investigating the relative roles of αβ and γδ T cells in the immunopathology of schistosomiasis found that mutant mice lacking γδ T cells display vigorous formation of egg granulomas similar to normal mice, which demonstrates that granuloma formation is not dependent on γδT cells (127).…”

Section: Innate γδ T Cells In Schistosomiasismentioning

confidence: 99%

T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

et al. 2020

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The parasitic worms, Schistosoma mansoni and Schistosoma japonicum, reside in the mesenteric veins, where they release eggs that induce a dramatic granulomatous response in the liver and intestines. Subsequently, infection may further develop into significant fibrosis and portal hypertension. Over the past several years, uncovering the mechanism of immunopathology in schistosomiasis has become a major research objective. It is known that T lymphocytes, especially CD4 + T cells, are essential for immune responses against Schistosoma species. However, obtaining a clear understanding of how T lymphocytes regulate the pathological process is proving to be a daunting challenge. To date, CD4 + T cell subsets have been classified into several distinct T helper (Th) phenotypes including Th1, Th2, Th17, T follicular helper cells (Tfh), Th9, and regulatory T cells (Tregs). In the case of schistosomiasis, the granulomatous inflammation and the chronic liver pathology are critically regulated by the Th1/Th2 responses. Animal studies suggest that there is a moderate Th1 response to parasite antigens during the acute stage, but then, egg-derived antigens induce a sustained and dominant Th2 response that mediates granuloma formation and liver fibrosis. In addition, the newly discovered Th17 cells also play a critical role in the hepatic immunopathology of schistosomiasis. Within the liver, Tregs are recruited to hepatic granulomas and exert an immunosuppressive role to limit the granulomatous inflammation and fibrosis. Moreover, recent studies have shown that Tfh and Th9 cells might also promote liver granulomas and fibrogenesis in the murine schistosomiasis. Thus, during infection, T-cell subsets undergo complicated cross-talk with antigen presenting cells that then defines their various roles in the local microenvironment for regulating the pathological progression of schistosomiasis. This current review summarizes a vast body of literature to elucidate the contribution of T lymphocytes and their associated cytokines in the immunopathology of schistosomiasis.

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“…γδΤ cells is one of the subsets of T-lymphocyte with a small number which was found in the recent 30 years, only accounted for 0.5%~5% of the total number of lymphocytes in peripheral blood of adults [1]. Recent studies [1][2][3][4][5] have found that the γδΤ cells in the body played an important role of antiinfection, anti-tumor, immune surveillance, immune regulation and maintenance of immune tolerance. In the past years, the γδΤ cells were separate by flow cytometry or magnetic cell separation technology, not only needing a lot of peripheral blood, but also requiring expensive equipment and complex operations.…”

Section: Introductionmentioning

confidence: 99%

A method for detecting intracellular IL-2 in γδT cells

Wang¹,

Hou²,

Duan³

et al. 2018

biomedicalresearch

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Objective: To establish a method for detecting intracellular IL-2 in human peripheral blood γδΤ cells. Methods: Healthy Human Peripheral Blood Mononuclear Cells (PBMCs) were isolated, then stimulated with low molecular peptide antigen of Mycobacterium tuberculosis (Mtb-Ag), and a high proportion of γδΤ cells was obtained. PBMCs and γδΤ cells were excited with phorbol myristate acetate(PMA) and incomycin (IM). Protein transportion inhibitors (Brefeldin A, BFA) were used to block the secretion of cytokines and saponins taken for membrane permeabilization. Flow cytometry was applied to detect the expression of CD69 in CD3 + T cells to explore the appropriate time of membrane permeabilization. Then flow cytometry was implemented to detect the expression of intracellular IL-2 in γδΤ cells. Analysis of variance (ANOVA) and least significant difference(LSD) test were conducted to determine the statistical difference. Results: Compared with those with 5 min and 25 min of membrane permeabilization, CD3 + T cells with 15 min has the highest expression of CD69 (87.82 ± 2.28%) (F=112.805, P<0.001). Compared with γδΤ group, γδΤ+PMA+IM group and PBMC+PMA+IM+BFA group, γδΤ cells with the stimulant of PMA, IM and blocker of BFA (γδΤ+PMA+IM+BFA) had the highest expression of intracellular IL-2 (50.65 ± 6.25%) (F=321.071, P<0.001). Conclusion: Flow cytometry is an appropriate method for the detection of intracellular IL-2 in γδΤ cells, and it may be applicable to detect other cytokines in γδΤ cells.

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Gamma delta T cells in non‐immune patients during primary schistosomal infection

Cited by 6 publications

References 32 publications

Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis

Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis

T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

A method for detecting intracellular IL-2 in γδT cells

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