Blockade of CD40-CD40 ligand (CD40L) costimulation has been shown to synergize with that of CTLA4/CD28-B7 to promote transplant tolerance. To date, however, CD28-B7 interactions have been prevented using B7-blocking reagents like CTLA4-Ig that inhibit CD28-B7 together with CTLA4-B7 interactions. In this study, we have tested anti-CD28 Abs to prevent selectively CD28-B7 interactions while preser...

IMPORTANCE Lymphocytic hypophysitis (LH) is a poorly understood autoimmune disorder of the pituitary gland. Symptoms include headache, pituitary dysfunction, visual disturbances, and neurological deficits. The diagnosis can be made based on clinical and biochemical findings, but for atypical presentations, no circulatory diagnostic biomarkers exist, and a pituitary biopsy is necessary for diagn...

C T LYMPHOCYTE-associated antigen 4 (CTLA4) blockade using the human anti-CTLA4 monoclonal antibody CP-675,206 has antitumor activity in melanoma (1). Blockade of CTLA4 binding to its B7 ligands results in disruption of peripheral immune tolerance and enhanced T cell activation (2), which can cause secondary autoimmune endocrinopathies, including hypophysitis and thyroiditis (1, 3, 4). We herei...

The role of B cells in the development of CD4+ regulatory T cells has been emphasized recently. Our previous studies have demonstrated that the antigen-presenting splenic B cells converted naïve CD4+CD25- T cells into CD4+CD25+Foxp3- T cells without additional cytokines or chemicals with regulatory activity and that referred to as Treg-of-B cells. The present study further showed that Treg-of-B...

The inhibitory receptor CTLA4 has a key role in peripheral tolerance of T cells for both normal and tumor-associated antigens. Murine experiments suggested that blockade of CTLA4 might have antitumor activity and a clinical experience with the blocking antibody ipilimumab in patients with metastatic melanoma did show durable tumor regressions in some patients. Therefore, a phase II study of ipi...

BACKGROUND AND AIM The connection between gene polymorphisms of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and primary biliary cholangitis (PBC) is still vague and blurred. The purpose of this study is to precisely estimate the association of the polymorphisms of CTLA4 with the risk of PBC by using a meta-analysis. METHODS PubMed and the Chinese National Knowledge Infrastructure (CNK...

Systemic lupus erythematosus (SLE) is an autoimmune disease that results in chronic inflammation of different organ systems. Several susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes has yet to be determined. The programmed cell death 1 gene (PDCD1), the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene, and the methyl-Cp...

DNA-based vaccination has emerged as a promising method of immunisation since the first demonstration of this technology. Improving the antibody responses is desirable for the protective efficacy and hence broad application of these vaccines. We examined the immunogenicity of a Plasmodium-based DNA vaccine that was targeted to antigen presenting cells by fusion to CTLA4. Fusion proteins compris...

Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4) play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of five CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with de novo malignancy in 1463 Chinese renal transp...

One of the most significant clinical advances in cancer immunotherapy to date has been the targeting of the immune “checkpoints” that inhibit effector T-cell function. Cytotoxic T lymphocyte-associated protein 4 (CTLA4), which was one among the first checkpoint regulators to be characterized, is transiently expressed by activated effector T cells and constitutively expressed on regulatory T cel...