The Journal of Immunology, Vol 156, Issue 7 2430-2435, Copyright © 1996 by American Association of Immunologists

ARTICLES

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

S Sriskandan, TJ Evans and J Cohen
Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

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.

This article has been cited by other articles:

				M. Unnikrishnan, D. M. Altmann, T. Proft, F. Wahid, J. Cohen, J. D. Fraser, and S. Sriskandan The Bacterial Superantigen Streptococcal Mitogenic Exotoxin Z Is the Major Immunoactive Agent of Streptococcus pyogenes J. Immunol., September 1, 2002; 169(5): 2561 - 2569. [Abstract] [Full Text] [PDF]

				W. W. S. Kum, S. B. Cameron, R. W. Y. Hung, S. Kalyan, and A. W. Chow Temporal Sequence and Kinetics of Proinflammatory and Anti-Inflammatory Cytokine Secretion Induced by Toxic Shock Syndrome Toxin 1 in Human Peripheral Blood Mononuclear Cells Infect. Immun., December 1, 2001; 69(12): 7544 - 7549. [Abstract] [Full Text] [PDF]

				H. Muller-Alouf, T. Proft, T. M. Zollner, D. Gerlach, E. Champagne, P. Desreumaux, C. Fitting, C. Geoffroy-Fauvet, J. E. Alouf, and J.-M. Cavaillon Pyrogenicity and Cytokine-Inducing Properties of Streptococcus pyogenes Superantigens: Comparative Study of Streptococcal Mitogenic Exotoxin Z and Pyrogenic Exotoxin A Infect. Immun., June 1, 2001; 69(6): 4141 - 4145. [Abstract] [Full Text] [PDF]

				S.-J. Won, W.-T. Huang, Y.-S. Lai, and M.-T. Lin Staphylococcal Enterotoxin A Acts through Nitric Oxide Synthase Mechanisms in Human Peripheral Blood Mononuclear Cells To Stimulate Synthesis of Pyrogenic Cytokines Infect. Immun., April 1, 2000; 68(4): 2003 - 2008. [Abstract] [Full Text] [PDF]

				D. M. McKay, J. Lu, S. Jedrzkiewicz, W. Ho, and K. A. Sharkey Nitric Oxide Participates in the Recovery of Normal Jejunal Epithelial Ion Transport Following Exposure to the Superantigen, Staphylococcus aureus Enterotoxin B J. Immunol., October 15, 1999; 163(8): 4519 - 4526. [Abstract] [Full Text] [PDF]

				J. J. Bright, C. Du, and S. Sriram Tyrphostin B42 Inhibits IL-12-Induced Tyrosine Phosphorylation and Activation of Janus Kinase-2 and Prevents Experimental Allergic Encephalomyelitis J. Immunol., May 15, 1999; 162(10): 6255 - 6262. [Abstract] [Full Text] [PDF]

				J. J. Lasarte, F. J. Corrales, N. Casares, A. Lopez-Diaz de Cerio, C. Qian, X. Xie, F. Borras-Cuesta, and J. Prieto Different Doses of Adenoviral Vector Expressing IL-12 Enhance or Depress the Immune Response to a Coadministered Antigen: the Role of Nitric Oxide J. Immunol., May 1, 1999; 162(9): 5270 - 5277. [Abstract] [Full Text] [PDF]

				C. S. Constantinescu, M. Wysocka, B. Hilliard, E. S. Ventura, E. Lavi, G. Trinchieri, and A. Rostami Antibodies Against IL-12 Prevent Superantigen-Induced and Spontaneous Relapses of Experimental Autoimmune Encephalomyelitis J. Immunol., November 1, 1998; 161(9): 5097 - 5104. [Abstract] [Full Text] [PDF]

				J. J. Bright and S. Sriram TGF-{beta} Inhibits IL-12-Induced Activation of Jak-STAT Pathway in T Lymphocytes J. Immunol., August 15, 1998; 161(4): 1772 - 1777. [Abstract] [Full Text] [PDF]

				D. Sekkai, F. Aillet, N. Israel, and M. Lepoivre Inhibition of NF-kappa B and HIV-1 Long Terminal Repeat Transcriptional Activation by Inducible Nitric Oxide Synthase 2 Activity J. Biol. Chem., February 13, 1998; 273(7): 3895 - 3900. [Abstract] [Full Text] [PDF]