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 schistosomiasis is mediated by CD4+ T helper lymphocytes sensitized to parasite egg antigens. However, CD8+ T cells have also frequently been 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 in 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-infected MHC class II mutant mice failed to form granulomas around parasite eggs. In contrast, infected MHC class I mutant mice displayed characteristic granulomatous lesions that were comparable to those in wild-type control mice. Moreover, lymphoid cells from MHC class II mutant mice were unable to react to egg antigens with either proliferative or cytokine [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, cells from MHC class I mutant mice exercised all these functions in a manner comparable with those from wild-type controls. These observations clearly demonstrate that schistosomal egg granulomas are mediated by MHC class II-restricted CD4+ T helper cells. They also suggest that CD8+ T cells do not become sensitized to egg antigens and play little role, if any, in the pathogenesis of schistosomiasis.
Hernandez
H J
HJ
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Wang
Y
Y
Tzellas
N
N
Stadecker
M J
MJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006099:Granuloma / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology
D016207:Cytokines; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II