Increased c-Fos/activator protein-1 confers resistance against anergy induction on antigen-specific T cell.
We have studied the contribution of c-Fos/activator protein-1 (AP-1) to antigen-specific T cell response with reference to T cell anergy by increasing c-Fos/AP-1 in vivo and in vitro. First, after injection of a high dose of staphylococcus enterotoxin B (SEB), clonal deletion of SEB-reactive V(beta)8(+) CD4 T cells occurred both in control B6 and H2-c-fos transgenic (fos) mice, whereas proliferation of T cells against SEB was profoundly depressed in B6 but not in fos mice. Second, the keyhole limpet hemocyanin-specific CD4 T(h)1 cell clone produced decreasing amounts of IL-2 in response to increasing amounts of concanavalin A (Con A) in vitro, whereas the decrease was less significant in the T(h)1 clones stably transfected with c-fos gene. Electrophoretic mobility shift assay with nuclear protein from the transformants showed that overexpression of the c-fos gene compensated the amounts of AP-1 in the nuclei of Con A-treated T(h)1 clones. Thus, increased c-Fos/AP-1 confers resistance against anergy induction on antigen-specific T cells.
Kawasaki
H
H
Faculty of Health Science, Department of Medicine, Third Division, Kobe University School of Medicine, Kobe 654, Japan.
Nakata
Y
Y
Suzuki
G
G
Chihara
K
K
Tokuhisa
T
T
Shiozawa
S
S
D000818:Animals; D004768:Enterotoxins / Q000276:immunology; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000502:physiology*
D004768:Enterotoxins; D007376:Interleukin-2; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; C031818:enterotoxin B, staphylococcal