Induction of specific nonresponsiveness in unprimed human T cells by anti-CD3 antibody and alloantigen.
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.
Anasetti
C
C
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Tan
P
P
Hansen
J A
JA
Martin
P J
PJ
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D017252:CD3 Complex; D002478:Cells, Cultured; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell