THE SIGNIFICANCE OF LOW BCL-2 EXPRESSION BY CD45RO-T-CELLS IN NORMAL INDIVIDUALS AND PATIENTS WITH ACUTE VIRAL-INFECTIONS - THE ROLE OF APOPTOSIS IN T-CELL MEMORY

The bcl-2 gene product has been shown to prevent apoptotic cell death. We have now investigated the bcl-2 protein expression by resting and activated mature T cell populations. Freshly isolated CD45RO+ T cells within CD4+ and CD8+ subsets expressed significantly less bcl-2 than C D45RO- (CD45RA+) T cells (p <0.001). When CD45RA+ T cells within both CD4+ and CD8+ subsets were activated in vitro, the transition to CD45R O phenotype was associated with a decrease in bcl-2 expression. Patien ts with acute viral infections such as infectious mononucleosis caused by Epstein-Barr virus infections or chickenpox, resulting from varice lla zoster virus infection, had circulating populations of activated C D45RO+ T cells which also showed low bcl-2 expression. In these patien ts, a significant correlation was seen between low bcl-2 expression by activated T cells and their apoptosis in culture (r = 0.94, p <0.001) . These results suggest that the primary activation of T cells leads t o the expansion of a population that is destined to perish unless resc ued by some extrinsic event. Thus the suicide of CD45RO+ T cells could be prevented by the addition of interleukin 2 to the culture medium w hich resulted in a concomitant increase in the bcl-2 expression of the se cells. Alternatively, apoptosis was also prevented by coculturing t he activated T lymphocytes with fibroblasts, which maintained the viab ility of lymphoid cells in a restinglike state but with low bcl-2 expr ession. The paradox that the CD45RO+ population contains the primed/me mory T cell pool yet expresses low bcl-2 and is susceptible to apoptos is can be reconciled by the observations that maintenance of T cell me mory may be dependent on the continuous restimulation of T cells, whic h increases their bcl-2 expression. Furthermore, the propensity of CD4 5RO+ T cells to extravasate may facilitate encounter with fibroblast-l ike cells in tissue stroma and thus be an important additional factor which promotes the survival of selected primed/memory T cells in vivo.