title: Expression of class II, but not class I, major histocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni.
abstract: 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.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Hernandez
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Tzellas
authors.forename: M J
authors.initials: MJ
authors.lastname: Stadecker
mesh_terms: 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
chemical_list: D016207:Cytokines; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II