T cell costimulation, particularly by the B7 family members B7-1 and B7-2, plays a critical role in regulating T cell-mediated immunity. Two molecules on T cells, CD28 and CTLA-4, are known to bind to B7. It has been suggested that CD28-B7 interaction promotes T cell response, whereas B7-CTLA-4 interaction downregulates T cell clonal expansion. However, the proposed responses of individual rece...

T cell activation through the T cell receptor (TCR) involves partitioning of receptors into discrete membrane compartments known as lipid rafts, and the formation of an immunological synapse (IS) between the T cell and antigen-presenting cell (APC). Compartmentalization of negative regulators of T cell activation such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is unknown. Recent cr...

It is generally acknowledged that cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4/CD152) plays a pivotal role in the regulation of T-cell activation and the establishment of self-tolerance in the periphery. CTLA-4-deficient (CTLA-4KO) mice develop a lymphoproliferative disorder and die within 4 weeks of birth, suggesting a role for CTLA-4 in T-cell homeostasis or the development and activit...

The inhibitory T-cell surface-expressed receptor, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which belongs to the class of cell surface proteins phosphorylated by extrinsic tyrosine kinases that also includes antigen receptors, binds the related ligands, B7-1 and B7-2, expressed on antigen-presenting cells. Conformational changes are commonly invoked to explain ligand-induced "trigge...

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T cell costimulation receptor that delivers inhibitory signals upon activation. Although the tyrosine-based motif ((165)YVKM) within its cytoplasmic tail has been shown to associate in vitro with Src homology 2 domain-containing tyrosine phosphatase (SHP-2) and phosphatidylinositol 3 kinase upon phosphorylation, the mechanism of negative signaling ...

Evidence indicates that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) may negatively regulate T cell activation, but the basis for the inhibitory effect remains unknown. We report here that cross-linking of CTLA-4 induces transforming growth factor beta (TGF-beta) production by murine CD4(+) T cells. CD4(+) T helper type 1 (Th1), Th2, and Th0 clones all secrete TGF-beta after antibody cr...

C Ytotoxic T lymphocyte-assodated molecule-4 (CTLA-4) is a lymphocyte cell surface receptor originally discovered in a search for molecules having a role in T cell cytotoxicity (1). This molecule is a member of the immunoglobulin superfamily and is homologous to another T cell surface receptor, CD28. Both CD28 and CTLA-4 bind the same counter-receptors, members of the B7 family on APCs. While t...

Recent studies indicate that CTLA-4 interaction with B7 ligands transduces an inhibitory signal to T lymphocytes. Mice homozygous for a null mutation in CTLA-4 have provided the most dramatic example of the functional importance of CTLA-4 in vivo. These animals develop a fatal lymphoproliferative disorder and were reported to have an increase in CD4(+) and CD8(+) thymocytes and CD4(-)CD8(-) thy...

The CTLA-4 pathway is a key regulator of T cell activation and a critical failsafe against autoimmunity. Although early models postulated that CTLA-4 transduced a negative signal, in vivo evidence suggests that CTLA-4 functions in a cell-extrinsic manner. That multiple cell-intrinsic mechanisms have been attributed to CTLA-4, yet its function in vivo appears to be cell-extrinsic, has been an on...

CTLA-4 encodes cytotoxic T lymphocyte-associated antigen-4, a cell-surface molecule providing a negative signal for T-cell activation. CTLA-4 gene polymorphisms have been widely studied in connection with genetic susceptibility to various autoimmune diseases, but studies have led to contradictory results in different populations. This case-control study sought to investigate whether CTLA-4 CT60...