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Amelioration of Autoimmune Reactions by Antigen-Induced Apoptosis of T Cells

  • Hugh I. McFarland
  • Jeffrey M. Critchfield
  • Michael K. Racke
  • John P. Mueller
  • Steven H. Nye
  • Stefen A. Boehme
  • Michael J. Lenardo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 383)

Abstract

Exposure of mature T cells to their specific antigen normally results in proliferation, but in the presence of high and repeated doses of antigen we have found that these same T cells undergo programmed cell death. The conditions required for antigen to induce the death of mature T cells include: an initial mitogenic stimulus that induces T cell responsiveness to growth lymphokines such as interleukin 2 (IL-2) or interleukin 4 (IL-4), T cell progression through the cell cycle, and finally strong T cell receptor (TCR) restimulation while still under the influence of growth lymphokine. Our data suggest that antigen-induced T cell death is part of a feedback regulatory loop which senses and controls the magnitude of the T cell response to antigen, that we have termed, “Propriocidal regulation.” Propriocidal regulation provides an explanation for the phenomenon of high dose suppression, and a mechanism for the peripheral deletion of T cells resulting in antigen-specific immunological tolerance. In this review, we will discuss data demonstrating the effeciveness of an immunotherapy based on the propriocidal mechanism to delete autoantigen-reactive T cells in experimental allergic encephalomyelitis (EAE), a mouse model for multiple sclerosis (MS).

Keywords

Myelin Basic Protein Adoptive Transfer Experimental Allergic Encephalomyelitis Cell Deletion Chronic Relapse Experimental Allergic Encephalomyelitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Hugh I. McFarland
    • 1
  • Jeffrey M. Critchfield
    • 2
  • Michael K. Racke
    • 3
  • John P. Mueller
    • 4
  • Steven H. Nye
    • 4
  • Stefen A. Boehme
    • 1
  • Michael J. Lenardo
    • 1
  1. 1.Laboratory of ImmunologyNational Institute of Allergy and Infectious Diseases National Institutes of HealthBethesdaUSA
  2. 2.Department of MedicineUniversity of California at San FranciscoSan FranciscoUSA
  3. 3.Department of NeurologyWashington University School of MedicineSt. LouisUSA
  4. 4.Alexion Pharmaceuticals Inc.New HavenUSA

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