BACKGROUND The inflammatory nature of atherosclerosis provides a broad range of potential molecular targets for atherosclerosis imaging. Growing interest is focused on targets related to plaque vulnerability such as the co-stimulatory molecules CD80 and CD86. We investigated in this preclinical proof-of-concept study the applicability of the CD80/CD86-binding fusion protein belatacept as a prob...

BACKGROUND In chronic lymphocytic leukemia lenalidomide causes striking immune activation, possibly leading to clearance of tumor cells. We conducted this study to investigate the mechanism of action of lenalidomide and the basis for its unique toxicities in chronic lymphocytic leukemia. DESIGN AND METHODS Patients with relapsed chronic lymphocytic leukemia were treated with lenalidomide 20 m...

A critical process during thymic development of the T cell repertoire is the induction of self-tolerance. Tolerance in developing T cells is highly dependent on medullary thymic epithelial cells (mTEC), and mTEC development in turn requires signals from mature single-positive thymocytes, a bidirectional relationship termed thymus crosstalk. We show that CD28-CD80/86 and CD40-CD40L costimulatory...

Functional T-cell responses are initiated by physical interactions between T-cells and antigen-presenting cells (APCs), including dendritic cells (DCs) and B-cells. T-cells are activated more effectively by DCs than by B-cells, but little is known about the key molecular mechanisms that underpin the particular potency of DC in triggering T-cell responses. To better understand the influence of p...

The structurally related T cell surface molecules CD28 and CTLA-4 interact with cell surface ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APC) and modulate T cell antigen recognition. Preliminary reports have suggested that CD80 binds CTLA-4 and CD28 with affinities (Kd values approximately 12 and approximately 200 nM, respectively) that are high when compared with other mol...

CD28 and CTLA-4 are prototypal co-stimulatory and co-inhibitory cell surface signaling molecules interacting with CD80/86, known to be critical for immune response initiation and regulation, respectively. Initial "bench-to-beside" translation, two decades ago, resulted in the development of CTLA4-Ig, a biologic that targets CD80/86 and prevents T-cell costimulation. In spite of its proven effec...

Chronic obstructive pulmonary disease (COPD) is an inflammation disorder and possibly an autoimmune disease. The components of the autoimmune response in the circulatory system are of considerable interest to clinicians. Because aberrations of costimulation status have been noted in COPD, the presence of autoantibodies to B7 costimulatory factor CD80 were investigated in a cohort of patients. R...

Previous studies have shown that the pan CD28/cytotoxic T lymphocyte antigen (CTL)A-4 antagonist CTLA4 immunoglobulin (Ig) inhibits eosinophilic airway inflammation in Schistosoma mansoni-sensitized and airway-challenged mice. In the present study, the importance of CD28 as well as the individual roles of CD80 and CD86 were examined in this system using wild-type and CD28 knockout (KO) mice. Un...

Thymic epithelial cells (TECs) help orchestrate thymopoiesis, and TEC differentiation relies on bidirectional interactions with thymocytes. Although the molecular mediators that stimulate medullary thymic epithelial cell (mTEC) maturation are partially elucidated, the signals that regulate cortical thymic epithelial cell (cTEC) homeostasis remain elusive. Using IL-7 reporter mice, we show that ...

Regulatory T cells (Tregs) are essential for tolerance to self and environmental Ags, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naive CD4 T cell-DC interactions. In this study, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs...