CTLA4 is an inhibitory regulator of immune responses. Therapeutic CTLA4 blockade enhances T cell responses against cancer and provides striking clinical results against advanced melanoma. However, this therapy is associated with immune-related adverse events. Paraneoplastic neurologic disorders are immune-mediated neurological diseases that develop in the setting of malignancy. The target oncon...

The main aim is to perform mutational analysis of CTLA4 gene Exon 1 in SLE patients. A total of 61 SLE patients fulfilling “American College of Rheumatology (ACR) criteria” and 61 controls were enrolled in this study. The region of CTLA4 gene exon 1 was amplified by using Step-down PCR technique. Extracted DNA of band 354 bp was sequenced to analyze mutations in the exon-1 of CTLA-4 gene. Furth...

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during ...

Murine dendritic cells (DCs) expressing indoleamine 2,3 dioxygenase (IDO) catabolize tryptophan and can suppress T cell responses elicited in vivo. Here, we identify specific subsets of splenic (CD11c+) dendritic cells competent to mediate IDO-dependent T cell suppression following CTLA4-mediated ligation of B7 molecules. IDO-competent DC subsets acquired potent and dominant T cell suppressive ...

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory mol...

Graves disease is complex autoimmune thyrotoxicosis. A number of genes may contribute to the development of the disorder. Some of them may be genes that encode cytotoxic T-lymphocyte-associated serine esterase-4 (CTLA4), subunit 2 of large multifunctional protease (LMP2), thyroid-stimulating hormone receptor (TSHR), and interleukin 1 receptor antagonist (IL1RN). We studied polymorphism of Ala17...

Immune checkpoints have been aggressively investigated for anti-cancer immunotherapy. The power of microbiota on the outcome this immunotherapy has attracted much attention. For example, intestinal microorganisms play a key role in effectiveness programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade. Additionally, short-chain fatty acids produced gut may ...

BALB/c mice are susceptible to progressive infection with Leishmania major due to the preferential development of CD4(+) T cells that secrete Th2 cytokines. Although Th2 cell development and susceptibility are disrupted by blockade of CD86 function early in infection, CD28-deficient BALB/c mice remain susceptible to leishmaniasis. We therefore examined whether the alternative CD86 ligand, CTLA4...

Adoptive transfer of peripheral blood-derived, melanoma-reactive CD8(+) cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with anti-CTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a bolus of enhanced IL-21-primed polyclonal antigen-specific CTL combined with CTLA4 blockade migh...

The enhanced osteogenesis of mesenchymal stem cells (MSCs) modified by expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been shown in previous studies, but the mechanism remains unknown. Here we found that the bone repair effect of CTLA4-modified MSCs in demineralized bone matrix (DBM) in a rabbit radius defect model was significantly better than that observed for unmodifie...