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. ...

Immune system dysfunction is one of the key features in onset and development of cancer and autoimmunity. Cytotoxic T-lymphocyte-antigen-4 (CTLA-4), as a leader immune checkpoint plays a crucial effects in the regulation of immune suppression and tolerance. In this review, role of CTLA-4 and its three important polymorphisms (SNP), CTLA-4 +49A/G, CTLA-4 CT60 A/G and CTLA-4 −318C/T in developmen...

PURPOSE Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) we...

We examined how cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates heterogeneous CD4(+) T cell responses by using experimental autoimmune encephalomyelitis (EAE), a CD4(+) T cell-mediated disease that is subject to regulation by CTLA-4. Disease incidence and severity were used as measures of in vivo CD4(+) T cell responses. The frequency, cytokine production, and reactivity of primed T cells w...

Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic...

OBJECTIVES Factors contributing to the development of systemic lupus erythematosus (SLE) remain largely unknown although are likely to include both environmental and genetic components. Studies on murine lupus have indicated a role for an antibody that blocks binding of cytotoxic T lymphocyte associated-4 (CTLA-4) to B7 on antigen presenting cells in the treatment of disease, suggesting that CT...

BACKGROUND Several lines of evidence approve that innate and adaptive immunity play key roles in the defense against visceral leishmaniasis (VL). The polymorphism within the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene alters its expression. OBJECTIVES The main aim of this study was to evaluate the polymorphism within the +49 position of the CTLA-4 gene of Iranian patients with VL in compar...

Cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) expressed at high levels by CD4(+) CD25(+) CD45RB(low) regulatory T cells (Treg) is essential to their homeostatic and immunoregulatory functions. However, its relevance to anti-inflammatory roles of Treg in the context of colitogenic innate immune response during pathogenic bacterial infections has not been examined. We showed earlier in Rag...

PURPOSE Acute anterior uveitis (AAU) is the most common form of uveitis and is thought to be autoimmune in nature. Recent studies have described genes that act as master controllers of autoimmunity. Protein tyrosine phosphatase type 22 (PTPN22) and Cytotoxic T lymphocyte antigen-4 (CTLA-4) are two of these genes, and single nucleotide polymorphisms (SNPs) in the genes encoding these molecules h...