CD40L IS IMPORTANT FOR INDUCTION OF, BUT NOT RESPONSE TO, COSTIMULATORY ACTIVITY - ICAM-1 AS THE 2ND COSTIMULATORY MOLECULE RAPIDLY UP-REGULATED BY CD40L

The CD40 ligand (CD40L):CD40 interaction plays an important role in th e activation of both T and B cells, However, the mechanisms by which t his interaction is involved in activation of T cells is still unclear, Here we show that CD40L is not essential for T cell response to TCR e ngagement if the APC have costimulatory activity, although it is essen tial for T cell mediated induction of such costimulatory activity, To determine the molecular basis of this activity, we have produced three mAbs that appear to recognize the costimulatory molecules rapidly ind uced by CD40L. Two of them recognize CD44H, which we showed to have CD 28-independent costimulatory activity for T cells, The molecule recogn ized by the remaining mAb is hereby identified as ICAM-1, Furthermore, ICAM-1-mediated costimulation is likely to serve for a function simil ar to that mediated by the B7:CD28 interaction, as targeted mutation o f CD28 renders T cell responses to Con A more dependent on ICAM-1.