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Title: Effect of treatments with cyclosporin A and anti-interferon-gamma antibodies on the mechanisms of immune tolerance in staphylococcal enterotoxin B primed mice
Authors: Kuschnaroff, L M ×
Valckx, Dirk
Goebels, Jozef
Rutgeerts, Omer
Heremans, Hubertine
Froyen, Guido
Waer, Mark #
Issue Date: Nov-1997
Series Title: Scandinavian journal of immunology vol:46 issue:5 pages:459-68
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.
ISSN: 0300-9475
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Nephrology
Molecular Genetics Section (-)
Laboratory of Immunobiology (Rega Institute)
Laboratory of Experimental Transplantation
Human Genome Laboratory
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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