title: Loss of Th1-associated function in peripheral T cells but not thymocytes in tolerance to major histocompatibility complex alloantigen.
abstract: Mice of the strains A.TH and A.TL were rendered neonatally tolerant to class II major histocompatibility complex (MHC) by the injection of (A.TH x A.TL)F1 spleen and bone marrow cells within 24 hr of birth. Spleen and thymus cells from adult tolerant mice bearing long-term surviving skin grafts were compared with those from normal mice for their in vitro reactivity towards the tolerogen. In a primary mixed lymphocyte reaction (MLR), spleen cells from normal mice proliferated in response to 'tolerogen', generated cytotoxic cells and produced interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) but no IL-4 or IL-5. In contrast, although spleen cells from tolerant mice proliferated and produced IL-2, they failed to generate cytotoxic cells or produce IFN-gamma but produced large amounts of IL-4 and IL-5. The loss of the ability of tolerant cells to generate cytotoxicity or IFN-gamma was profound in that no activity was detected in a secondary MLR and mRNA for IFN-gamma could not be detected by reverse transcription polymerase chain reaction (RT-PCR). To see whether the alteration in function occurred centrally or peripherally, thymus cells from normal and tolerant mice were tested for function. Normal thymocytes produced IFN-gamma, IL-4 and IL-5 in a primary MLR and generated cytotoxic cells in a secondary MLR. In contrast to spleen cells, thymus cells from tolerant mice retained their ability to generate IFN-gamma or cytotoxic cells in response to tolerogen. Overall the results point to a profound switch in peripheral tolerogen-specific responses from a Th 1-biased response in normal mice to a Th2-biased response in tolerant mice and suggest that the alteration in function is post thymic.
authors.affiliation: Department of Cell and Structural Biology, University of Manchester, U.K.
authors.forename: P J
authors.initials: PJ
authors.lastname: Wood
authors.forename: I A
authors.initials: IA
authors.lastname: Cossens
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D007108:Immune Tolerance / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D016207:Cytokines; D007519:Isoantigens