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).
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McFarland, H.I. et al. (1995). Amelioration of Autoimmune Reactions by Antigen-Induced Apoptosis of T Cells. In: Atassi, M.Z., Bixler, G.S. (eds) Immunobiology of Proteins and Peptides VIII. Advances in Experimental Medicine and Biology, vol 383. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1891-4_18
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DOI: https://doi.org/10.1007/978-1-4615-1891-4_18
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