objective: celiac disease (cd) is developed via autoimmune reactions against gluten which is mainly found in grains. although hla dqb1 locus is the most important genetic susceptibility to cd, some other variants such as a49g and g1359t of ctla4 and cd14 genes respectively have been proposed as cd predisposing genetic factors in many various studies. we aimed to assess possible roles of a49g an...

PURPOSE Cytotoxic T lymphocyte antigen 4 (CTLA4), a key negative regulator of T-cell activation, is targeted by the antibody tremelimumab to release potentially useful antitumor activity. EXPERIMENTAL DESIGN This phase II trial investigated tremelimumab as a second-line treatment for patients with metastatic gastric and esophageal adenocarcinomas. Tremelimumab was given every 3 months until s...

Idd5.1 regulates T1D susceptibility in nonobese diabetic (NOD) mice and has two notable candidate genes, Ctla4 and Icos. Reduced expression of one of the four CTLA-4 isoforms, ligand-independent CTLA-4 (liCTLA-4), which inhibits in vitro T cell activation and cytokine production similarly to full-length CTLA-4 (flCTLA-4), has been hypothesized to increase type 1 diabetes (T1D) susceptibility. H...

STAT4(-/-) mice have impaired type 1 T cell differentiation, whereas STAT6(-/-) mice fail to generate type 2 responses. The role of type 1 and type 2 T cell differentiation in acute cardiac allograft rejection and in the induction of tolerance was examined in wild-type, STAT4(-/-), and STAT6(-/-) recipients. All recipients rejected the grafts promptly. Analysis of in situ cytokine gene expressi...

Chronic autoimmune thrombocytopenic purpura (AITP) is characterized by platelet-specific autoantibody production that is influenced by enhanced antiplatelet T-helper cell reactivity. Costimulatory signals are absolutely required for T-cell activation and play key roles in the decision between tolerance and immunity. In this study we cultured T cells isolated from patients with chronic AITP to i...

BACKGROUND Receptor occupancy (RO) assays measure drug target engagement, and are used as pharmacodynamic (PD) biomarkers. RO assays are commonly performed by flow cytometry and often require multiplexing for assessment of multiple PD biomarkers when specimen volumes are limited. We present multiplexed RO assays for an IGF1R-EGFR bispecific antibody (Bs-Ab) and a CTLA4-Ig recombinant fusion pro...

T cell-mediated immunity is critical in resistance against Leishmania parasites, and T cell activation requires signals provided by costimulatory molecules. Herein we evaluated the role of costimulatory molecules on cytokine production and T cell surface molecule expression by peripheral blood mononuclear cells (PBMC) from cutaneous leishmaniasis (CL) patients. PBMC from CL patients were stimul...

B cell-activating factor belonging to the TNF family (BAFF) blockade prevents the onset of disease in systemic lupus erythematosus (SLE)-prone NZB/NZW F(1) mice. To determine the mechanism of this effect, we administered a short course of TACI-Ig with and without six doses of CTLA4-Ig to 18- to 20-wk-old NZB/NZW F(1) mice and evaluated the effect on B and T cell subsets and on anti-dsDNA Ab-pro...

Introduction: A variety of genetic predisposing factors and environmental factors are known to influence the pathogenesis of type-1 diabetes (T1D). This study intended to investigate the association of cytotoxic T-lymphocyte associated protein 4 (CTLA4) and interleukin 2 receptor subunit alpha (IL2RA) gene polymorphisms with type 1 diabetes in children of northwest of Iran. Methods: Genomic DNA...

| Since the regulatory approval of ipilimumab in 2011, the field of cancer immunotherapy has been experiencing a renaissance. This success is based on progress in both preclinical and clinical science, including the development of new methods of investigation. Immuno-oncology has become a sub-specialty within oncology owing to its unique science and its potential for substantial and long-term c...