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

Activation-inducible lymphocyte immune-mediatory molecule (AILIM) is an ind ucible cell surface glycoprotein expressed on thymocytes and activated lymp hocytes. Specific monoclonal antibody to rat AILIM induced the cell aggrega tion of a rat thymoma cell line and ConA-activated splenocytes. In the pres ent study, we identified the primary structure of two species of rat AILIM by expression cloning. We also cloned mouse and human AILIM homologues and the predicted amino acid sequences were identical to those of the inducible costimulator ICOS/CRP-1, which belongs to the CD28/ CTLA4 family. Although the human and mouse AILIM/ ICOS molecule is localized on T-cells, the majo r population of AILIM/ICOS-positive cells in rat splenocyte was CD45RA-posi tive B-cells. The expression level of AILIM/ICOS on T-cells was relatively low; however, its expression was drastically induced by the treatment with PMA. plus Ca-ionophore or the engagement of CD3 and these costimulatory mol ecules. Almost all T-cells exhibited potency as to its expression. Function al analysis of AILIM/ICOS demonstrated that AILIM-mediated costimulation wa s relatively weak compared to that of human. (C) 2000 Academic Press.