Anergy and cytokine-mediated suppression as distinct superantigen-induced tolerance mechanisms in vivo.
Recombinant-activating gene 2 (RAG-2-/-) T cell receptor-transgenic mice repeatedly injected with the superantigen staphylococcal enterotoxin A entered a tolerant state in which splenic CD4+ T cells produced little interleukin (IL)-2, interferon gamma, or IL-4. This state resulted from a combination of both clonal anergy and cytokine-mediated immunosuppression. The anergy persisted for at least 3 wk and could be distinguished from the suppression by a decrease in IL-2 production per cell, a block in the activation of early response kinases, and a failure to be reversed with anti-transforming growth factor (TGF)-beta. Full suppression lasted for only 1 wk and involved both IL-10 and TGF-beta, but required additional unknown molecules for optimal effect. These experiments show that complex in vivo interactions of multiple peripheral tolerance mechanisms can now be dissected at both the cellular and molecular levels.
Miller
C
C
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0420, USA.
Ragheb
J A
JA
Schwartz
R H
RH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D007376:Interleukin-2; C499308:Rag2 protein, mouse; D018089:Superantigens; D016212:Transforming Growth Factor beta; C064655:V(D)J recombination activating protein 2; D016753:Interleukin-10; D015847:Interleukin-4; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma; D017871:Calcium-Calmodulin-Dependent Protein Kinases