Immunologic tolerance in T lymphocytes is maintained through both thymic and peripheral contributions. One peripheral tolerance mechanism is the induction of T cell anergy, a form of nonresponsiveness resulting from incomplete T cell activation, such as stimulation through the TCR in the absence of costimulation. Recent reports have suggested that engagement of the inhibitory receptor CTLA-4 by...

The costimulatory signal provided to T cells through CTLA-4-ligand interactions is required for T cell activation resulting in increased interleukin 2 (IL-2) production in vitro, but its role in the production of IL-4 and other cytokines is unclear and few in vivo studies have been performed to confirm results of in vitro experiments. We have examined the in vivo effects of blocking CTLA-4 liga...

Expression of the CTLA-4 gene is absolutely required for immune homeostasis, but aspects of its molecular nature remain undefined. In particular, the characterization of the soluble CTLA-4 (sCTLA-4) protein isoform generated by an alternatively spliced mRNA of CTLA4 lacking transmembrane-encoding exon 3 has been hindered by the difficulty in distinguishing it from the transmembrane isoform of C...

Hypophysitis that develops in cancer patients treated with monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; an inhibitory molecule classically expressed on T cells) is now reported at an incidence of approximately 10%. Its pathogenesis is unknown, in part because no pathologic examination of the pituitary gland has been reported to date. We analyzed at autopsy...

In addition to static structures, the Unified Modelling Language (UML) supports the specification of dynamic properties of objects by means of statechart and sequence diagrams. Moreover, the upcoming UML 2.0 standard defines several kinds of actions to specify invocations, computations and the access of structural features. The formal specification technique compositional Temporal Logic of Acti...

PURPOSE CTLA-4 is one of the most fundamental immunosuppressive cotykines which belongs to the immunoglobulin super-family, and is expressed mainly on activated T cells. Previous studies have reported the existence of CTLA4 60G/A and CTLA4 -1661A/G polymorphism in cancers. However, the effects remain conflicting. Hence, we performed a meta-analysis to investigate the association between these p...

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) modifying agents have been involved in the development of intestinal inflammation, especially therapeutic monoclonal antibodies directed against CTLA-4. Here we report the appearance of a severe stricturing Crohn's disease-like colitis in a patient with a kidney allograft who was treated with belatacept, a recombinant CTLA-4-Ig fusion protein.

Mice deficient for the expression of CTLA-4 develop a lethal lymphoproliferative syndrome and multiorgan inflammation leading to death at about 4 wk of age. Here we show that RAG2-deficient mice reconstituted with CTLA-4-deficient bone marrow do not develop a lymphoproliferative syndrome despite lymphocyte infiltration mainly into pericardium and liver. Moreover, RAG2-deficient mice reconstitut...

T lymphocytes play an essential role in the defense against several pathogens and in tumor immune surveillance. However, T cells can also trigger autoimmune diseases and acute allograft rejection. Therefore, understanding the mechanisms of activation of T lymphocytes may help develop novel immunomodulators for therapeutic purposes. T-cell activation results from recognition by the T-cell recept...

Immunotherapy with tumor lysate-loaded dendritic cells (DCs) is one of the most promising strategies to induce antitumor immune responses. However, the antitumor activity of cytotoxic T cells may be restrained by their expression of the inhibitory T-cell coreceptor cytotoxic T lymphocyte antigen-4 (CTLA-4). By relieving this restraint, CTLA-4-bloc...