Human CD8(+) T cells expressing HLA-DR and CD28 show telomerase activity and are distinct from cytolytic effector T cells

Cycling lymphocytes may express the enzyme telomerase which is involved in maintenance of telomere length and cell proliferation potential. In CD8(+) T cells freshly isolated from peripheral blood, we found that in vivo cycli ng cells expressed HLA-DR. Furthermore, CD28-positive cells are known to ha ve longer telomeres than CD28-negative T cells. Therefore we used HLA-DR- a nd CD28-specific antibodies to sort CD8(+) T cells and measure telomerase a ctivity ex vivo. Relatively high levels of telomerase activity were found i n HLA-DR/CD28 double-positive cells. In contrast, HLA-DR-negative and CD28- negative cells had almost no telomerase activity. In summary, HLA-DR expres sion correlates with proliferation, and CD28 expression with proliferative potential. We have previously identified that ex vivo cytolytic CD8+ T cell s are CD56 (NCAM) positive. Here we show that HLA-DR+ cells were rarely CD5 6(+) and vice versa. This demonstrates that telomerase-expressing and cytol ytic CD8(+) T cells can be separated on the basis of the cell surface marke rs HLA-DR and CD56. Thus, activated CD8(+) T cells specialize and exert dis tinct functions correlating with surface molecule expression.