Regulation of granulomatous inflammation in murine schistosomiasis. V. Antigen-induced T cell-derived suppressor factors down-regulate proliferation and IL-2, but not IL-4, production by CD4+ effector T cells.
Acute murine schistosomiasis mansoni is characterized by a vigorous CD4+ delayed-type hypersensitivity T cell-mediated granulomatous immune response to deposited parasite eggs. During the chronic stage of infection the granulomatous response is spontaneously down-modulated by Ag-specific Ts cells and their soluble factors. Recently, we established an in vitro model system whereby soluble egg Ag (SEA)-induced acute and chronic infection-derived Ts cells suppressed the proliferation and IL-2 production of acute infection effector delayed-type hypersensitivity T cells. In the present study, culture supernatants harvested from the induced Ts cell cultures were found to suppress, in a non-cytotoxic manner, the SEA-mediated proliferation and IL-2, but not IL-4 production of acute infection CD4+ splenic T cells. Northern blot analysis confirmed that the factor-mediated suppression of IL-2 in the acute infection cells occurred at the transcriptional level as IL-2 mRNA was suppressed within 10 h of SEA stimulation. The acute (A-TseF) and chronic (C-TseF) infection-derived effector suppressor factors were found to be Ag-specific both in production and elicitation of function, and acted without MHC restriction. Moreover, the A-TseF and C-TseF molecules bear binding sites for SEA and an A-TseF was also shown to bind anti-SEA antibodies. Positive selection by flow cytometry showed that the TseF molecules are produced by Ag-stimulated CD4+ acute or chronic infection splenic cells and that CD4+ cells are the target of the suppression.
Fidel
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PL
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201.
Boros
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DL
D000818:Animals; D000909:Antibodies, Helminth / Q000378:metabolism; D000947:Antigens, Helminth / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D015745:Granuloma, Foreign-Body / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013491:Suppressor Factors, Immunologic / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007376:Interleukin-2; D012333:RNA, Messenger; D013491:Suppressor Factors, Immunologic; D015847:Interleukin-4