Optimal T cell activation requires engagement of CD28 with its counterligands B7-1 and B7-2. Inducible costimulator (ICOS) is the third member of the CD28/CTLA4 family that binds a B7-like protein, B7RP-1. Administration of ICOS-Ig attenuates T cell expansion following superantigen (SAg) administration, but fails to regulate either peripheral deletion or anergy induction. ICOS-Ig, but not CTLA4...

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...

Initiation of diabetes in NOD mice can be mediated by the costimulatory signals received by T cells. The ICOS is found on Ag-experienced T cells where it acts as a potent regulator of T cell responses. To determine the function of ICOS in diabetes, we followed the course of autoimmune disease and examined T cells in ICOS-deficient NOD mice. The presence of ICOS was indispensable for the develop...

OBJECTIVE Proliferation and migration of smooth muscle cells (SMCs) and migration and accumulation of monocytes and T cells are landmark events in the development of arteriosclerosis. SMC proliferation in the intima induces interruption of blood flow and results in ischemia and graft rejection. Inducible costimulator (ICOS) is a major costimulator of T cell activation. However, the effect of co...

Over the last 15 years, the inducible T cell co-stimulator (ICOS) has been implicated in various immune outcomes, including the induction and regulation of Th1, Th2, and Th17 immunity. In addition to its role in directing effector T cell differentiation, ICOS has also been consistently linked with the induction of thymus-dependent (TD) antibody (Ab) responses and the germinal center (GC) reacti...

A novel costimulatory molecule expressed on activated T cells, inducible costimulator (ICOS), and its ligand, B7-related protein-1 (B7RP-1), were recently identified. ICOS costimulation leads to the induction of Th2 cytokines without augmentation of IL-2 production, suggesting a role for ICOS in Th2 cell differentiation and expansion. In the present study, a soluble form of murine ICOS, ICOS-Ig...

Inducible costimulator (ICOS) has been suggested to perform an important role in T helper cell type 2 (Th2) responses, germinal center formation, and isotype switching. The role of ICOS in chronic Th2 responses was studied in a nematode model with the filarial parasite, Brugia malayi. Contrary to expectations, we did not observe a significant defect in IL-4-producing Th2 cells in ICOS-/- mice o...

The studies performed to date analyzed the overall participation of the inducible costimulator (ICOS) in model diseases, but did not yield information on the nature and function of ICOS-expressing T cells in vivo. We examined ICOS(+) T cells in the secondary lymphoid organs of nonmanipulated mice, in the context of an "unbiased" immune system shaped by environmental antigens. Using single cell ...

Plasmacytoid dendritic cells (pDCs) have the potential to prime CD4(+) T-cells to differentiate into IL-10-producing T regulatory cells through preferential expression of inducible co-stimulatory ligand (ICOS-L). Although pDCs produce cytokines such as type-I IFNs, TNF-α, or IL-6 accompanying up-regulation of ICOS-L expression during activation in response to toll-like receptor (TLR)-ligands or...

While the ligand of inducible co-stimulator (ICOS), B7 homologous protein, is widely expressed in somatic cells, B7-1 and B7-2 expression is mainly limited to lymphoid organs. Thus, the activation of T cells through ICOS without a CD28-mediated signal may occur in physiological situations. In order to gain a better understanding of the role of the ICOS co-stimulatory signal in immune responses,...