The inducible costimulator CD278 (ICOS) is similar to human CD28 (24% homology), and plays an analogous role in the T cell activation process. Unlike CD28, CD278 is only expressed on activated T cells. Secondary signaling through CD28 or CD278 results in discrete cytokine secretion profiles by the activated T cells (1). Engagement of CD152 (CTLA-4) anergizes cells costimulated with either CD28 and CD278 (2). Signaling through CD278 is particularly important in progression of TH2 immune response (5). The receptor for human CD278 (ICOS) is CD275 (GL50, ICOS L), a member of the B7 family sharing ~20% homology with CD80 (B7-1) and CD86 (B7-2) (3). Two RNA splice variants exist for this molecule, differing only in the cytoplasmic domain (4). Blockade of the CD278-CD275 interaction in mice improves allograft survival (6) and reduces EAE (7).