CTLA4-Ig–Based Bifunctional Costimulation Inhibitor Blocks CD28 and ICOS Signaling to Prevent T Cell Priming and Effector Function

Identification and characterization of rat AILIM/ICOS, a novel T-cell costimulatory molecule, related to the CD28/CTLA4 family.

Activation-inducible lymphocyte immuno-mediatory molecule (AILIM) is an inducible cell surface glycoprotein expressed on thymocytes and activated lymphocytes. Specific monoclonal antibody to rat AILIM induced the cell aggregation of a rat thymoma cell line and ConA-activated splenocytes. In the present study, we identified the primary structure of two species of rat AILIM by expression cloning....

Targeting T cell costimulation to prevent atherothrombosis.

Inflammation plays a key role in atherogenesis and precipitation of atherothrombosis. Immune cells, including macrophages and T cells, infiltrate the affected vascular wall, and inflammation drives build-up of atherosclerotic plaques.1–3 This concept of immune activation in atherosclerosis has become accepted, but specific therapy directed at inflammatory mechanisms is yet lacking.4 T cell acti...

Staying alive: T cell costimulation, CD28, and Bcl-xL.

Enhancement of CD8+ T cell responses by ICOS/B7h costimulation.

Although the recently identified ICOS/B7h costimulatory counterreceptors are critical regulators of CD4(+) T cell responses, their ability to regulate CD8(+) responses is unclear. Here we report using a tumor-rejection model that ectopic B7h expression can costimulate rejection by CD8(+) T cells in the absence of CD4(+) T cells. Although responses of naive T cells were significantly augmented b...

AILIM/ICOS signaling induces T-cell migration/polarization of memory/effector T-cells.

AILIM/ICOS has critical roles in the regulation of T-cell differentiation and effector T-cell function in various immune responses. The counter-ligand for AILIM/ICOS, B7h, is widely expressed in not only lymphoid tissue and antigen-presenting cells, but also in fibroblast and endothelial cells in various organs. Here, we demonstrate that activated human T-cells migrate beneath TNF-alpha-treated...