Involvement of CTLA-4 in T-cell anergy induced by staphylococcal enterotoxin A in vitro.

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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Xu GL,Zhu XH,Guo B,Wu YZ

doi

10.1016/j.molimm.2004.03.001

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

1-8

issue

1

eissn

0161-5890

issn

1872-9142

pii

S0161589004000513

journal_volume

41

pub_type

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