1. Involvement of CTLA-4 in T-cell anergy induced by staphylococcal enterotoxin A in vitro
- Author
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Gui-lian Xu, Xi-Hua Zhu, Bo Guo, and Yuzhang Wu
- Subjects
CD3 Complex ,T-Lymphocytes ,Immunology ,chemical and pharmacologic phenomena ,Biology ,Lymphocyte Activation ,Clonal deletion ,Cell Line ,Enterotoxins ,Immune system ,CD28 Antigens ,Antigens, CD ,Superantigen ,Humans ,CTLA-4 Antigen ,Molecular Biology ,Clonal Anergy ,Superantigens ,Clonal anergy ,T-cell receptor ,CD28 ,hemic and immune systems ,Antigens, Differentiation ,CTLA-4 ,CD80 - Abstract
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.
- Published
- 2003