Anergy and Cytokine-mediated Suppression as Distinct Superantigen-induced Tolerance Mechanisms In Vivo

doi:10.1084/jem.190.1.53

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J. Exp. Med., Volume 190, Number 1, July 5, 1999 53-64
Copyright © 1999 by The Rockefeller University Press.

Anergy and Cytokine-mediated Suppression as Distinct Superantigen-induced Tolerance Mechanisms In Vivo

Carla Miller^a, Jack A. Ragheb^a, and Ronald H. Schwartz^a
^a From the Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0420

Correspondence to: Ronald H. Schwartz

Recombinant-activating gene 2 (RAG-2^-/-) T cell receptor–transgenicmice repeatedly injected with the superantigen staphylococcalenterotoxin A entered a tolerant state in which splenic CD4⁺T cells produced little interleukin (IL)-2, interferon ${gamma}$ , orIL-4. This state resulted from a combination of both clonalanergy and cytokine-mediated immunosuppression. The anergy persistedfor at least 3 wk and could be distinguished from the suppressionby a decrease in IL-2 production per cell, a block in the activationof early response kinases, and a failure to be reversed withanti–transforming growth factor (TGF)-ß. Full suppressionlasted for only 1 wk and involved both IL-10 and TGF-ß,but required additional unknown molecules for optimal effect.These experiments show that complex in vivo interactions ofmultiple peripheral tolerance mechanisms can now be dissectedat both the cellular and molecular levels.

Key Words: CD4⁺ T cell receptor transgenic cells, early response kinaseactivation, interleukin 2, interleukin 10, transforming growthfactor ß

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