The Journal of Experimental Medicine
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Journal of Experimental Medicine, Vol 172, 1691-1700, Copyright © 1990 by Rockefeller University Press

ARTICLES

Induction of specific nonresponsiveness in unprimed human T cells by anti-CD3 antibody and alloantigen

C Anasetti, P Tan, JA Hansen and PJ Martin
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.

Fresh peripheral blood mononuclear cells exposed to alloantigen for 3-8 d in the presence of anti-CD3 antibodies showed no response after restimulation with cells from the original donor but remained capable of responding to third-party donors. Antigen-specific nonresponsiveness was induced by both nonmitogenic and mitogenic anti-CD3 antibodies but not by antibodies against CD2, CD4, CD5, CD8, CD18, or CD28. Nonresponsiveness induced by anti-CD3 antibody in mixed leukocyte culture was sustained for at least 34 d from initiation of the culture and 26 d after removal of the antibody. Anti-CD3 antibody also induced antigen-specific nonresponsiveness in cytotoxic T cell generation assays. Anti-CD3 antibody did not induce nonresponsiveness in previously primed cells. Nonresponsiveness induced by anti-CD3 did not appear to be associated with suppressor cell activation. Thus, co- stimulation of the T cell receptor-CD3 complex on unprimed T cells with a fluid phase anti-CD3 antibody and allogenic major histocompatibility complex antigens can induce either clonal anergy or clonal deletion. These results suggest novel approaches for achieving transplantation tolerance.
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