CTLA-4 is a potent inhibitor of T cell activation, primarily upon binding to its costimulatory ligands (B7.1 and B7.2) expressed on APCs. However, variants of CTLA-4 can also function independently of B7 molecules. 1/4CTLA-4 is a highly conserved isoform encoded by exons 1 and 4 of the Ctla4 gene that lacks the ligand-binding and the transmembrane domains, and as yet, its function is not known....

Recently, "ipilimumab," an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. "CTLA-4" is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTLA-4 inhibitory signal, allowing the immune system to react to cancer cells. Du...

Cytotoxic T lymphocyte antigen-4 (CTLA-4/CD152) is a member of the CD28 family of T cell effector antigens. Current belief, based primarily on results from gene-deleted mice, is that CTLA-4 promotes suppression of T cell proliferation. In this manuscript, Mark Slifka and colleagues compare antiviral responses of unmanipulated virus-specific CTLA-4 and CTLA-4 T cells. The results of this work su...

CTLA-4 is a negative regulator for T cell activation and plays an important role in down-regulating immune responses and the maintenance of peripheral tolerance. The effect of initial treatment with anti-CTLA-4 mAb on murine acute and chronic graft-versus-host diseases (GVHD) induced by transfer of either C57BL/6 or BALB/c splenocytes into F1 recipient mice has been investigated. The treatment ...

BACKGROUND Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by downregulating T cell activation. The most studied +49A>G polymorphism of the CTLA-4 gene has been associated with several autoimmune diseases. However, little is known about the association between this functional polymorphism of CTLA-4 and cancer prognosis. OBJECT...

CTLA-4 proteins contribute to the suppressor function of regulatory T cells (Tregs), but the mechanism by which they do so remains incompletely understood. In the present study, we assessed CTLA-4 protein function in both Tregs and conventional (Tconv) CD4 T cells. We report that CTLA-4 proteins are responsible for all 3 characteristic Treg functions of suppression, TCR hyposignaling, and anerg...

CTLA-4 plays an important role in the down-regulation of activated T cells and in the establishment of peripheral tolerance. It has been hypothesized that CTLA-4 on the cell surface signals directly into T cells during primary immune responses, resulting in intrinsic T cell down-regulation. It is not known, however, whether CTLA-4 directly inhibits the less intense activating signals received b...

Successful immune cell control requires a delicate balance of positive and negative regulatory signals. Costimulatory pathways involving molecules such as CD28, inducible costimulator (ICOS), 4-1BB, and CD40L are essential coactivators of proliferation, cytokine production, and cell migration. To balance these signals, cell surface molecules like Fas, tumor necrosis factorreceptor (TNFR), and p...

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...

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...