CD45RO(-CELLS BUT NOT CD45RA(+) NAIVE T-CELLS CAN BE EFFICIENTLY ACTIVATED BY REMOTE CO-STIMULATION WITH B7() MEMORY T)

Co-stimulatory signals are absolutely required for T cell activation a fter TCR - MHC-peptide interaction. The most important co-stimulatory signal known so far is mediated by the interaction of CD28 on T cells with B7 on APC. Here we demonstrate that the co-stimulatory signal fro m the B7 molecule does not necessarily have to come from the same cell which presents antigen. Titration curves obtained by limiting the amo unt of anti-CD3 mAb suggests that the same amount of TCR - CD3 cross-l inking is required for full T cell activation whether B7 is present on the same or on another cell, but that the kinetics of T cell activati on is slower when B7 is present on a separate cell from the primary si gnal. Finally and most importantly we also show that CD45RO+ memory T cells, but not CD45RA+ naive T cells, can be efficiently activated whe n B7 is expressed on bystander cells. These findings imply that co-sti mulatory activation requirements of B7 are more stringent for naive th an for memory T cells, which could be an important mechanism involved in the maintenance of self-tolerance.