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

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 gamma delta T cell receptor (TCR) has not been determined. In this study we utilized mutant mice that lack either alpha beta or gamma delta T cells as a result of gene targeting to investigate the relative roles of alpha beta and gamma delta 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 delta mutant mice (lacking gamma delta 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 alpha and TCR beta mutant mice (lacking alpha beta T cells) were unable to form granulomas. Moreover, mesenteric lymph node cells from TCR delta mutant and control mice responded strongly to egg antigens in vitro, while TCR alpha and beta mutant mice did not. Our studies show that in schistosomiasis granuloma formation and proliferative responses to egg antigens are strictly dependent on alpha beta T cells. They also suggest that gamma delta T cells by themselves can neither mediate a granulomatous inflammation, nor significantly modify one mediated by alpha beta T cells.