Th2-type granuloma development in acute murine schistosomiasis is only partly dependent on CD4+ T cells as the source of IL-4.
Schistosome granulomas produce IL-4, important for Th2 granuloma expression. We defined the origins of IL-4 within these granulomas and the role of IL-4-producing CD4(+) T cells in Th2 granuloma development. Dispersed granuloma cells spontaneously produced IL-4 independently of T cells, whereas IL-5 production was T cell dependent. Granuloma IL-4 mRNA localized to the non-T cells and IL-5 to T cells. Granuloma CD4(+) T and NK cells, but not B cells produced IL-4 and IL-5 in vitro. B cell-/- mice generated Th2 granulomas that produced IL-4 and IL-5 normally. Granuloma eosinophils expressed no IL-4 or IL-5 mRNA. Granulomas in WWv mast cell-deficient mice lacked mast cells. The dispersed granuloma cells from WWv mice released IL-4 only after T cell stimulation, suggesting that mast cells influenced the constitutive component of IL-4 production. Rag-1 animals (T/B/NK T cell deficient) given schistosomiasis after reconstitution with splenocytes from naive mice produced Th2 granulomas. Mice reconstituted to create selective CD4(+) T cell IL-4 knockout animals developed eosinophilic granulomas that made IL-4. Thus, granulomas contain several cell types that produce IL-4. Mast cells are not needed to form Th2 granulomas, but influence IL-4 release. Th2 granuloma development in schistosomiasis is only partly dependent on IL-4-producing CD4(+) T cells.
Metwali
Ahmed
A
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.
de Andres
Belen
B
Blum
Arthur
A
Elliott
David
D
Li
Jie
J
Qadir
Khurram
K
Sandor
Matyas
M
Weinstock
Joel
J
D000818:Animals; D000941:Antigens / Q000378:metabolism; D000954:Antigens, Surface; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D016654:Genes, RAG-1; D006099:Granuloma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D008212:Lymphocyte Depletion; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*; D018800:Thy-1 Antigens / Q000378:metabolism
D000941:Antigens; D000954:Antigens, Surface; D015848:Interleukin-5; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D015847:Interleukin-4