EXPRESSION OF CLASS-II, BUT NOT CLASS-I, MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES IS REQUIRED FOR GRANULOMA-FORMATION IN INFECTION WITH SCHISTOSOMA-MANSONI

Previous studies have suggested that granulomatous inflammation in sch istosomiasis is mediated by CD4(+) T helper lymphocytes sensitized to parasite egg antigens. However, CD8(+) T cells have also frequently be en associated with the immune response to schistosome eggs. To examine more precisely the role of CD4(+) and CD8(+) T cells in the pathology of the schistosomal infection, we used mice with targeted mutations i n major histocompatibility complex (MHC) class II or class I molecules . These mutations lead, respectively, to the virtual absence of CD4(+) and CD8(+) T cells. The results clearly show that schistosome-infecte d MHC class II mutant mice failed to form granulomas around parasite e ggs. In contrast, infected MHC class I mutant mice displayed character istic granulomatous lesions that were comparable to those in wild-type control mice. Moreover, lymphoid cells from MHC class IT mutant mice were unable to react to egg antigens with either proliferative or cyto kine [interferon-gamma, interleukin (IL)-4, IL-10] responses; nor were they able to present egg antigens to specifically sensitized CD4(+) T helper cells from infected syngeneic control mice. By comparison, cel ls from MHC class I mutant mice exercised all these functions in a man ner comparable with those from wild-type controls. These observations clearly demonstrate that schistosomal egg granulomas are mediated by M HC class II-restricted CD4(+) T helper cells. They also suggest that C D8(+) T cells do not become sensitized to egg antigens and play little role, if any, in the pathogenesis of schistosomiasis.