CD45RO+ memory T cells but not CD45RA+ naive T cells can be efficiently activated by remote co-stimulation with B7.

Co-stimulatory signals are absolutely required for T cell activation after 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 from the B7 molecule does not necessarily have to come from the same cell which presents antigen. Titration curves obtained by limiting the amount of anti-CD3 mAb suggests that the same amount of TCR-CD3 cross-linking 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 activation is slower when B7 is present on a separate cell from the primary signal. Finally and most importantly we also show that CD45RO+ memory T cells, but not CD45RA+ naive T cells, can be efficiently activated when B7 is expressed on bystander cells. These findings imply that co-stimulatory activation requirements of B7 are more stringent for naive than for memory T cells, which could be an important mechanism involved in the maintenance of self-tolerance.