Effect of treatments with cyclosporin A and anti-interferon-gamma antibodies on the mechanisms of immune tolerance in staphylococcal enterotoxin B primed mice
(1997) Scandinavian Journal of Immunology — Vol. 46, n° 5, p. 459-468 (1997)
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- 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 (SEE) in BALB/c mice. After SEE immunization, tolerance was mainly achieved through deletion and anergy of SEE-reactive V beta 8(+) T cells. Association of CsA treatment with SEE led to a greater decrease of the percentage of V beta 8(+)CD4(+) lymphocytes in the spleen and an abolition of clonal anergy. In contrast, treatment of SEE 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 SEE priming, splenic mRNA levels of IFN-gamma and IL-4 were decreased by either CsA and anti-IFN-gamma Abs, whereas Fast, Ecl-2, p. 53, and c-myc levels were not influenced by either treatment. However, SEE-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 SEE 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 SEE 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.
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Kuschnaroff, L., Valckx, D., Goebels, J., Rutgeerts, O., Heremans, H., Froyent, G., & Waer, M. (1997). Effect of treatments with cyclosporin A and anti-interferon-gamma antibodies on the mechanisms of immune tolerance in staphylococcal enterotoxin B primed mice. Scandinavian Journal of Immunology, 46(5), 459-468. https://doi.org/10.1046/j.1365-3083.1997.d01-152.x (Original work published 1997)