Evidence for repression of IL-2 gene activation in anergic T cells.
The induction of clonal anergy in a T cell inhibits IL-2 secretion because of the development of a proximal signal transduction defect. Fusion of anergic murine T cells to human Jurkat T leukemia cells and formation of heterokaryons failed to result in a complementation of this signaling defect and restoration of murine IL-2 mRNA inducibility. Instead, signal transduction to the human IL-2 gene became disrupted. Heterokaryons formed by the fusion of anergic murine T cells to normal murine T cells also failed to accumulate intracellular IL-2 protein in response to stimulation either with the combination of CD3 and CD28 mAbs or with ionomycin plus a protein kinase C-activating phorbol ester. The results argue against a loss-of-function signaling defect as the sole basis for clonal anergy induction and document the presence of a dominant-acting repressor molecule that inhibits signal transduction to the IL-2 gene within viable anergic T cells.
Telander
D G
DG
Department of Medicine and Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Malvey
E N
EN
Mueller
D L
DL
D000818:Animals; D001483:Base Sequence; D002459:Cell Fusion; D002460:Cell Line; D017635:Clonal Anergy / Q000187:drug effects / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005816:Genetic Complementation Test; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D012097:Repressor Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation