Bacterial superantigen-induced human lymphocyte responses are nitric oxide dependent and mediated by IL-12 and IFN-gamma

Sriskandan, S., Evans, T. J. and Cohen, J. (1996) Bacterial superantigen-induced human lymphocyte responses are nitric oxide dependent and mediated by IL-12 and IFN-gamma. Journal of Immunology, 156(7), pp. 2430-2435. (PMID:8786301)

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Bacterial superantigens cause marked proliferation of T cells and release of lymphokines. Nitric oxide, derived from the conversion of L-arginine to L-citrulline, inhibits this activation in murine cells. We have now investigated the roles of IL-12, IFN-gamma, lymphotoxin-alpha, and nitric oxide during superantigen-induced human lymphocyte activation. Lymphocyte activation was determined by measurement of proliferative responses and lymphokine release. Both toxic shock syndrome toxin-1 from Staphylococcus aureus and recombinant streptococcal pyrogenic exotoxin A induced proliferation and production of IFN-gamma, lymphotoxin-alpha, and IL-12 by human mononuclear cells in a time-dependent fashion. The release of IFN-gamma was abrogated by a neutralizing Ab to IL-12, but lymphocyte proliferative responses were unaffected. A neutralizing Ab to IFN-gamma prevented the release of lymphotoxin-alpha, but did not affect proliferation. The neutralization of lymphotoxin-alpha using two different Abs did not affect IFN-gamma release or proliferation. In contrast to previous findings in mice, the arginine analogue, NG-monomethyl-L-arginine, significantly inhibited both proliferation and lymphokine release by superantigen-stimulated human cells. Thus, the release of lymphotoxin-alpha by lymphocytes following superantigen stimulation is dependent upon the presence of IFN-gamma; the IFN-gamma response is in turn under the control of IL-12. There is no evidence that nitric oxide plays an inhibitory role during superantigen-mediated human lymphocyte activation. Indeed, arginine is a prerequisite for such activation.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Evans, Professor Tom
Authors: Sriskandan, S., Evans, T. J., and Cohen, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN (Online):1550-6606

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