Reduced CD3-mediated protein tyrosine phosphorylation in anergic CD4+ and CD8+ T cells.
Mice inoculated i.v. with superantigens exhibit long lived Ag-specific T cell tolerance. An in vitro model for this phenomenon is the ensuing unresponsiveness of Th1 T cell clones activated via the TCR/CD3 complex in the absence of co-stimulation. We have previously demonstrated alterations in TCR-mediated early protein tyrosine phosphorylation events in Th1 clones anergic for IL-2 production. In this study, we demonstrate unresponsiveness in CD4+ and CD8+ T cells from V beta 8.1 transgenic mice inoculated i.v. with the superantigen Mls-1a. The unresponsiveness of both CD4+ and CD8+ T cells involves defective IL-2 production upon restimulation, with CD4+ T cells exhibiting an additional defect in IL-2 utilization. The transgenic model allowed study of T cell signaling in a relatively homogeneous population of unresponsive cells without elaborate purification of Ag-reactive populations. Both CD4+ and CD8+ T cells exhibit altered tyrosine phosphorylation of two protein substrates upon CD3-mediated restimulation. The substrates involved, p38 and p75, are of identical size to substrates similarly affected in anergic Th1 clones. Altered tyrosine phosphorylation is therefore closely associated with defective IL-2 production in these three anergic T cell types, and may play a role in the maintenance of anergy.
Bhandoola
A
A
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Cho
E A
EA
Yui
K
K
Saragovi
H U
HU
Greene
M I
MI
Quill
H
H
D000818:Animals; D017252:CD3 Complex / Q000502:physiology*; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D002478:Cells, Cultured; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D016747:Minor Lymphocyte Stimulatory Antigens; D011506:Proteins; D014443:Tyrosine