Human naive T cells are preferentially stimulated by crosslinking of CD3 and CD45RA with monoclonal antibodies.

To analyze the role of CD45 molecules in CD3-mediated activation of T cells, we analyzed the effect of crosslinking different CD45 isoforms with mAbs on the proliferation of various T cell subsets in vitro. Crosslinking of CD3 and CD45RA molecules with the mAb 2H4 or WR16 resulted in the preferential stimulation of enriched naive (CD45RA+) T cells, whereas crosslinking of CD3 alone led to stimulation of enriched memory (CD45RO+) T cells. In contrast, proliferation of memory T cells was not enhanced by additional crosslinking with the memory T cell marker CD45RO. To induce the costimulatory effect on naive T cells, an intense crosslinking of the TcR/CD3 complex and CD45RA molecules by immobilized secondary antibody is necessary because enhanced proliferation did not occur when the antibodies were directly immobilized. The same differences in reactivity of CD45RA-enriched naive and CD45RO-enriched memory T cell subset could be shown by using a mAb to common CD45, indicating that the effects are not mediated by a particular antibody or by binding to different epitopes. The CD45RA-induced differences in proliferation of naive and memory T cells could not be abolished by the addition of exogenous IL2. In contrast, naive T cells were more responsive to exogenous IL2 than memory T cells independently of CD45RA crosslinking, indicating that IL2 is not responsible for the observed differences in T cell proliferation.