Involvement of CTLA-4 in T-cell anergy induced by staphylococcal enterotoxin A in vitro.
Superantigens, like staphylococcal enterotoxin A (SEA), induce a strong proliferative response followed by clonal deletion of a substantial portion of defined V(beta) T-cells. The remaining cells display in vitro anergy. Anergy is a major mechanism to ensure antigen-specific tolerance in T-lymphocyte in the adult. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T-cell activation and immune regulation. While increasing data further suggested a role for CTLA-4 in regulating T-cell tolerance in vivo, the mechanism by which CTLA-4 influences T-lymphocyte tolerance is unclear. In the present study, we established an in vitro anergy model using superantigen SEA as the anergizing agents and examined CD3, CD28 and CTLA-4 expression of anergic T-cells in response to SEA rechallenge. It is found that anergic T-cell fails to produce the autocrine growth factor interleukin-2 (IL-2) upon stimulation, and addition of exogenous IL-2 can reverse the anergic state. Both TCR/CD3 complex and CD28 expression is not reduced in anergic cells during whole immune response, but the expression of CTLA-4 on the cell surface is enhanced dramatically in the late stages of an immune response. Using CTLA-4/B7-blocking agent, we found T-cell anergy was aborted and anergic T-cells restored the ability to proliferate and produce IL-2, suggesting that CTLA-4 may play a critical role in the induction of T-cell anergy.
Xu
Gui-Lian
GL
Institute of Immunology PLA, Third Military Medical University, Gaotanyan, Shapingba, Chongqing 400038, PR China.
Zhu
Xi-Hua
XH
Guo
Bo
B
Wu
Yu-Zhang
YZ
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D060908:CTLA-4 Antigen; D002460:Cell Line; D017635:Clonal Anergy; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004768:Enterotoxins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal