introduction : cytotoxic t-cell lymphocyte antigen 4 (ctla-4) is a member of the superfamily of immunoglobulins that are mainly expressed by activated t cells. it is established that blockade of ctla-4 receptors leads to the enhancement of an immune response. different polymorphisms of the ctla-4 gene have been described which cause increased susceptibility to various malignancies such as lymph...

CTLA-4 is an essential inhibitor of T cell immune responses. At steady state, most CTLA-4 resides in intracellular compartments due to constitutive internalisation mediated via a tyrosine based endocytic motif (YVKM) within the cytoplasmic domain. This domain is highly conserved in mammals suggesting strong selective pressure. In contrast, the C-terminal domain varies considerably in non-mammal...

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...

The role of CTLA-4 in regulatory T cell (Treg) function is not well understood. We have examined the role of CTLA-4 and its relationship with the transcription factor FoxP3 using a model of Treg induction in human peripheral blood. Activation of human CD4(+)CD25(-) T cells resulted in the appearance of a de novo population of FoxP3-expressing cells within 48 h. These cells expressed high levels...

CTLA-4 is thought to inhibit effector T cells both intrin-sically, by competing with CD28 for B7 ligands, and ex-trinsically, through the action of regulatory T cells (Tregs). We studied in vivo responses of normal and CTLA-4–deficient Ag-specific murine effector CD4 + T cells. We directly demonstrate that effector T cell-restricted CTLA-4 inhibits T cell responses in a cell-extrinsic manner. C...

To examine the relationship between cytotoxic T lymphocyte antigen-4 (CTLA-4) expression and esophageal carcinoma prognosis, CTLA-4 expression was immunohistochemically detected in paraffin-embedded primary tumor specimens from 158 patients with esophageal cancer. CTLA-4 was detected in the cytoplasm and cell membranes of esophageal cancer cells and in interstitial lymphocytes. In univariate an...

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor on T cells essential for maintaining T cell homeostasis and tolerance to self. Mice lacking CTLA-4 develop an early onset, fatal breakdown in T cell tolerance. Whether this autoimmune disease occurs because of the loss of CTLA-4 function in regulatory T cells, conventional T cells, or both is unclear. We show here that lack of ...

CTLA-4 gene is one of the strongest locus of genetic susceptibility to autoimmune thyroid diseases. The aim of the present study was to investigate surface expression of CTLA-4 on peripheral T cells in homozygotes AA and GG at position +49 of CTLA-4 gene in children with Hashimoto's thyroiditis and in healthy controls. Blood samples were obtained from 100 children: 45 with Hashimoto's thyroidit...

CD8+ cytotoxic T lymphocytes contribute to viral and autoimmune myocarditis and cardiac allograft rejection. The role of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 as a negative regulator of CD4+ T cells is well defined, yet CTLA-4 regulation of CD8+ T cells is less clear. We studied CTLA-4 regulation of cytotoxic T lymphocytes in a transgenic model of CD8+ T-cell-mediated myocarditis. ...

Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic c...