Coreceptors CD28 and cytotoxic T lymphocyte antigen (CTLA)-4 have opposing effects on TcR/CD3 activation of T cells. While CD28 enhances and CTLA-4 inhibits activation, the underlying molecular basis of these effects has yet to be established. In this context, ganglioside and cholesterol enriched membrane microdomains (rafts, GEMs) serve as centers of signaling in T cells. Although CD28 can pro...

Immunosuppression may contribute to cancer progression, in which regulatory T (T-reg) cells have been demonstrated to play important roles. We investigated whether anti-CD25 (alpha-CD25) monoclonal antibody (mAb) and anti-cytotoxic T lymphocyte-associated antigen-4 (alpha-CTLA-4) mAb could augment in vitro proliferation and cytotoxic activity against cancer cell lines of lymphokine-activated ki...

Cytokine-induced killer (CIK) cells are in vitro-expanded cells harboring potent toxicity against tumor cells. Recently, it was identified that the cytotoxicity and proliferation of CIK cells are restricted by a prolonged CIK cell culture period. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) serves a negative role in T cell activation and proliferation. This study aims to determine wheth...

The capsular polysaccharides (caps-PS) of Streptococcus pneumoniae are classified as thymus-independent antigens. Nevertheless, T lymphocytes can modulate the antibody response to caps-PS. In this study, we show that anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) treatment, along with administration of caps-PS to BALB/c mice, resulted in a dose-dependent generation of a strong caps-PS...

The anti–CTL-associated antigen 4 (anti–CTLA-4) antibody ipilimumab is the first agent to show improved survival in a randomized phase III trial that enrolled patients with metastatic melanoma. Studies are ongoing to identify mechanisms that elicit clinical benefit in the setting of anti–CTLA-4 therapy. We previously reported that treated patients had an increase in the frequency of T cells exp...

The importance of the B7/CD28/CTLA-4 molecules has been established in studies of antigenpresenting cell-derived B7 and its interaction with the T cell costimulatory molecule CD28. CTLA-4, a T cell surface glycoprotein that is related to CD28, can also interact with B7-1 and B7-2. However, less is known about the function of CTLA-4, which is expressed at highest levels after activation. We have...

Single domain human immunoglobulin fold-based biomolecules Simon E. Hufton Target Quest B.V., University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands We have developed human immunoglobulin fold containing proteins as alternative binding ligands to antibodies. Firstly, we have evaluated cytotoxic T lymphocyte associated antigen 4 (CTLA-4) as a protein scaffold. CTLA-4 is...

Despite their common ability to activate intracellular signaling through CD80/CD86 molecules, cytotoxic T lymphocyte antigen 4 (CTLA-4)-Ig and CD28-Ig bias the downstream response in opposite directions, the latter promoting immunity, and CTLA-4-Ig tolerance, in dendritic cells (DCs) with opposite but flexible programs of antigen presentation. Nevertheless, in the absence of suppressor of cytok...

Cancer immunotherapy relies on the ability of the immune system to target tumor-specific antigens to generate an immune response. This initial response requires both binding of the MHC/antigen peptide to T-cell receptor complex, along with a second costimulatory signal created by the binding of CD28 on the T cell, with B7 located on the antigen-presenting cell. Regulatory checkpoints, such as c...

  Background :Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an important negative regulator of T-cell responses. The -1722TC polymorphism of the CTLA-4 gene may be associated with systemic lupus erythematosus (SLE) risk, but related results from previous studies have been inconsistent. We carried out a meta-analysis to assess this association more precisely.   Methods : A systematic s...