Altered antigen receptor signaling in anergic T cells from self-tolerant T-cell receptor beta-chain transgenic mice.
T-cell tolerance to the minor lymphocyte-stimulating antigen Mls-1a in a T-cell receptor (TcR) V beta 8.1 transgenic line of mice is maintained by both clonal deletion and clonal anergy. Approximately 20-50% of peripheral CD4+ (but not CD8+) T cells isolated from these mice are anergic and fail to proliferate following TcR ligation. We have examined key events in T-cell signaling in peripheral T cells isolated from these mice. In this report, we show that the anergic CD4+ T cells did not mobilize calcium or express receptors for interleukin 2 (IL-2) following TcR ligation. However, the cells retained viability and functional potential because stimulation with phorbol 12-myristate 13-acetate and ionomycin bypassed the block in receptor-mediated signaling and induced IL-2 receptor expression and proliferation of the anergic cells.
Blackman
M A
MA
Howard Hughes Medical Institute, Denver, CO.
Finkel
T H
TH
Kappler
J
J
Cambier
J
J
Marrack
P
P
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology; D002118:Calcium / Q000032:analysis; D002872:Chromosome Deletion; D003433:Crosses, Genetic; D015870:Gene Expression / Q000187:drug effects; D006183:H-2 Antigens / Q000235:genetics; D007108:Immune Tolerance; D015759:Ionomycin / Q000494:pharmacology; D046911:Macromolecular Substances; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000954:Antigens, Surface; D015704:CD4 Antigens; D006183:H-2 Antigens; D046911:Macromolecular Substances; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium