title: Effect of treatments with cyclosporin A and anti-interferon-gamma antibodies on the mechanisms of immune tolerance in staphylococcal enterotoxin B primed mice.
abstract: The authors were interested to investigate the effect of Cyclosporin A (CsA), known to block interleukin-2 (IL-2) production, or of anti-interferon-gamma antibodies (anti-IFN-gamma Abs) in a model of T cell tolerance induced by the injection of the superantigen Staphylococcal Enterotoxin B (SEB) in BALB/c mice. After SEB immunization, tolerance was mainly achieved through deletion and anergy of SEB-reactive V beta 8+ T cells. Association of CsA treatment with SEB led to a greater decrease of the percentage of V beta 8+ CD4+ lymphocytes in the spleen and an abolition of clonal energy. In contrast, treatment of SEB primed mice with anti-IFN-gamma Abs resulted in an increased percentage of V beta 8+ CD4+ cells without affecting the induction of clonal anergy. The authors found that 1-2 h after SEB priming, splenic mRNA levels of IFN-gamma and IL-4 were decreased by either CsA and anti-IFN-gamma Abs, whereas FasL, Bcl-2, p. 53, and c-myc levels were not influenced by either treatment. However, SEB-induced IL-2 and IL-10 mRNA expression was suppressed only by CsA, whereas tumour necrosis factor-alpha (TNF-alpha) was decreased only by anti-IFN-gamma Abs. To investigate whether the effect of CsA on the tolerance mechanisms was related to suppression of IL-2, CsA was administered together with recombinant IL-2. Whereas anergy was not influenced, the decreased percentage of V beta 8+ CD4+ cells seen in CsA-treated animals in the second week after SEB injection was partially corrected by the administration of IL-2. Experiments involving bromodeoxiuridine incorporation revealed that the latter effect of IL-2 was mainly due to a correction of the defective proliferation of V beta 8+ T cells after SEB injection in CsA-treated mice. These results suggest that the effect of CsA and anti-IFN-gamma Abs on tolerance mechanisms are in part explained by their action on cytokines.
authors.affiliation: Laboratory for Experimental Transplantation, Rega Institute, University of Leuven, Belgium.
authors.forename: L M
authors.initials: LM
authors.lastname: Kuschnaroff
authors.forename: D
authors.initials: D
authors.lastname: Valckx
authors.forename: J
authors.initials: J
authors.lastname: Goebels
authors.forename: O
authors.initials: O
authors.lastname: Rutgeerts
authors.forename: H
authors.initials: H
authors.lastname: Heremans
authors.forename: G
authors.initials: G
authors.lastname: Froyent
authors.forename: M
authors.initials: M
authors.lastname: Waer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D017635:Clonal Anergy / Q000187:drug effects; D017637:Clonal Deletion / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007108:Immune Tolerance / Q000187:drug effects*; D007114:Immunization; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D004768:Enterotoxins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D012333:RNA, Messenger; D018089:Superantigens; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D016572:Cyclosporine