AILIM/ICOS: Its Expression and Functional Analysis with Monoclonal Antibodies

Abstract

Activation-inducible lymphocyte immuno-mediatory molecule (AILIM/ICOS) is the third member of the co-stimulatory molecule CD28/CTLA-4 (CD152) family, and an inducible cell surface glycoprotein expressed on lymphocytes following activation. To determine the expression profile of the molecule, we generated monoclonal antibodies (MAbs) against human, rat, and mouse AILIM/ICOS. None of the MAbs bound to AILIM/ICOS of other species. The numbers of AILIM/ICOS-positive cells among human peripheral blood mononuclear cells (PBMC), and rat and mouse splenocytes were very low (0.5, 0.4, and 1.2%, respectively), and the cells included many CD4-positive T cells except in the case of rat. Rat AILIM/ICOS-positive cells among splenocytes included many CD45RA-positive B cells, although the expression on lymph node cells was similar to that on human PBMC and mouse splenocytes. Among rat thymocytes, the AILIM/ICOS expression was mainly localized on CD4- and CD8-double positive T cells. The binding of AILIM/ICOS to B7h-Ig, which is the ligand-Fc chimeric protein, was inhibited by all AILIM/ICOS-specific MAbs except for SG430. The potency of the co-stimulatory activity of CD3 and AILIM/ICOS as to T-cell proliferation was found to be substantial in human. Interestingly, the levels of stimulation with the two types of MAbs were equal to that with CD3 and CD28 despite the different functions of the two MAbs in the AILIM/ICOS-B7h interaction. On the other hand, the potencies in rat and mouse, although two independent MAbs were tested, were relatively lower than that of CD28-mediated co-stimulation.