Induction of interleukin 12 responsiveness is impaired in anergic T lymphocytes.
The cytokine, interleukin 12 (IL-12), stimulates both natural killer cells and T cells to proliferate and to secrete interferon gamma (IFN-gamma). The T cell proliferative response to IL-12 must be induced and is evident after T cell receptor-mediated stimulation. As reported here, tolerant CD4+ T cells and clones, that are anergic for IL-2 production, are also anergic for induction of the proliferative response to IL-12. Murine T helper 1 clones tolerized in vitro, as well as anergic CD4+ T cells isolated from mice tolerized to the Mls-1a antigen (Ag) in vivo, demonstrated defective induction of proliferation to IL-12 upon restimulation with Ag. IL-12-enhanced production of IFN-gamma was observed in both control and anergic cells after Ag/antigen-presenting cell (APC) activation, although total IFN-gamma secretion by anergic cells was less than that produced by control cells, even in the presence of IL-12. These data indicate that T cell clonal anergy results in profound inhibition of proliferative responses, since the autocrine growth factor, IL-2, is not produced, and the APC-derived cytokine, IL-12, is not an effective stimulus for anergic T cell proliferation.
Quill
H
H
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Bhandoola
A
A
Trinchieri
G
G
Haluskey
J
J
Peritt
D
D
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D017635:Clonal Anergy; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12; D007376:Interleukin-2 / Q000096:biosynthesis; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015704:CD4 Antigens; D006133:Growth Substances; D007376:Interleukin-2; D007378:Interleukins; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12; D007371:Interferon-gamma