ICAM-2 provides a costimulatory signal for T cell stimulation by allogeneic class II MHC.

To examine the functional role of intercellular adhesion molecule (ICAM)-2 (CD102) in antigen presentation to T cells, the I-E(d)-transfected murine fibroblastic L cell line RT10.3 (H-2(k)) was transfected with murine ICAM-1 or ICAM-2 and tested for their abilities to stimulate C3H/He (H-2(k)) splenic T cells. The expression of ICAM-1 or ICAM-2 on RT10.3 cells significantly increased the stimulation of T cells in an LFA-1 (CD11a/CD18)-dependent manner as determined by thymidine incorporation. This enhanced T cell response was also observed when combinations of untransfected RT10.3 cells and ICAM-1- or ICAM-2-transfected L cells were used as stimulators, indicating that ICAM-1 and ICAM-2 deliver a costimulatory signal instead of merely enhanced T cell adhesion to antigen presenting cells. The T cells stimulated with ICAM-transfected RT10.3 in the primary response vigorously responded to BALB/c (H-2(d)) spleen cells in a secondary allogeneic stimulation. In contrast, T cells stimulated with untransfected RT10.3 in the primary response did not respond to BALB/c spleen cells in the secondary response. Significant secondary responses to a third party stimulator, C57BL/6 spleen cells (H-2(b)), were observed regardless of ICAM expression on RT10.3 cells in the primary stimulation. These results indicate that ICAM-2 as well as ICAM-1 not only enhance antigen presentation mediated by allogeneic class II MHC but also provide a costimulatory signal to T cells. This costimulatory signal may be important in the aversion of an anergic state.