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 HUVEC and display morphological polarization via AILIM/ICOS signaling. AILIM/ICOS stimulation, in the absence of antigen stimulation, also induced T-cell polarization. Importantly, AILIM/ICOS-mediated polarization was evident in CD4+CD45RO+ memory T-cells and generated Th1 cells, but not in CD4+CD45RA+ naive T-cells and generated Th2 cells. Furthermore, AILIM/ICOS signaling is involved in transendothelial migration of Th1 cells, but not Th2 cells. Our data suggest that AILIM/ICOS-B7h interactions play an important role in the endothelium in controlling the entry of memory/effector T-cells into inflamed tissues in the periphery.