T cells expressing the γδ T cell receptor are not required for egg granuloma formation in schistosomiasis

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Abstract
Immunopathology in schistosomiasis consists of a granulomatous response around parasite eggs. It has been established that granuloma formation is mediated by CD4+ T helper cells. However, the role of T cells bearing the γδ T cell receptor (TCR) has not been determined. In this study we utilized mutant mice that lack either αβ or γδ T cells as a result of gene targeting to investigate the relative roles of αβ and γδ T cells in the induction of immunopathology related to schistosomiasis. Mutant and control mice were infected with Schistosoma mansoni and granuloma formation as well as lymph node cell proliferative responses to egg antigens were analyzed after 8 weeks. TCR δ mutant mice (lacking γδ T cells) displayed vigorous formation of egg granulomas that were not significantly different from those observed in normal controls, both in terms of granuloma size and cellular composition. In contrast, TCR α and TCR β mutant mice (lacking αβ T cells) were unable to form granulomas. Moreover, mesenteric lymph node cells from TCR δ mutant and control mice responded strongly to egg antigens in vitro, while TCR α and β mutant mice did not. Our studies show that in schistosomiasis granuloma formation and proliferative responses to egg antigens are strictly dependent on αβ T cells. They also suggest that γδ T cells by themselves can neither mediate a granulomatous inflammation, nor significantly modify one mediated by αβ T cells.