INDUCTION AND DETECTION OF APOPTOSIS IN HUMAN PERIPHERY BLOOD T-CELLS

Freshly isolated, human peripheral blood T (PBT) cells are resistant t o induction of apoptosis. In this study, however, we have shown that a lthough small numbers of monocytes (Mo) are required for PBT cells to proliferate optimally in response to mitogenic challenge, a relatively higher percentage of Mo results in a significant decrease in PHA-, bu t not ConA-induced T-cell proliferation. Interestingly, the decrease i n T-cell proliferation correlated to an increase in apoptotic cell dea th. Moreover, ConA-induced PET-cells underwent apoptosis in the presen ce of PHA-pretreated Mo, suggesting a key role of monocyte activation in this system. This apoptosis-promoting effect of activated Mo appear ed to depend on contact or close proximity between Mo and PET-cells, r ather than via soluble mediators. Despite an increase in apoptosis by the presence of high numbers of Mo, PHA-stimulated PET-cells released IL-2 at elevated levels proportional to the increasing numbers of Mo i n cultures. They also expressed activation marker CD69 and the IL-2R-g amma chain on the cell surface at comparable or higher levels in the p resence of high versus low numbers of Mo. These data suggest that PET- cells can embark on a normal early phase of activation prior to underg oing apoptosis, thereby providing a model system to study how T-cells are committed to either proliferation or activation-induced apoptosis. (C) 1997 Elsevier Science B.V.