DIFFERENTIAL ROLE FOR IL-2 AND IL-15 IN THE INHIBITION OF APOPTOSIS IN SHORT-TERM ACTIVATED HUMAN-LYMPHOCYTES

Interleukin (IL)-15 is a newly described cytokine with properties simi lar to IL-2. Even though it does not share sequence homology with IL-2 , both cytokines bind to the same receptor with the noted exception of a cytokine specific alpha-chain. In this study the authors compared I L-2 and IL-15 to determine their ability to rescue short term activate d lymphocytes (phytohaemagglutinin stimulation of peripheral blood mon onuclear cells for 6 days, followed by expansion in medium containing IL-2 for 2 days) from apoptotic cell death. The authors found that bot h IL-2 and IL-15 can inhibit induction of apoptosis in this experiment al model with similar time and dose kinetics. On mRNA or protein level s induction of pro- and anti-apoptotic gene products like fast, bcl-2, or bar with minor effects on fas/Apo-1 or bcl-x(L) was observed under culture conditions with both IL-2 and IL-15. Next, it was found that phytohaemagglutinin (PHA) blasts were less responsive (in terms of cel lular proliferation and prevention from apoptosis) to IL-2 if signals through the alpha-chain were blocked, with no effect on beta-chain spe cific monoclonal antibodies (MoAb). By contrast, IL-15 was less effect ive in induction of cellular proliferation and prevention of apoptosis if IL-2R beta-chain specific MoAb were added to cell cultures. Testin g intracellular signalling induced by IL-2 or IL-15, the authors found identical changes in tyrosine phosphorylation patterns in PHA blasts cultured in medium or under IL-2 or IL-15 stimulation. By contrast, th ey found consistent differences if PHA stimulated peripheral blood mon onuclear cells (PBMC) were expanded in medium containing IL-15 (instea d of IL-2). These IL-15 expanded PHA blasts showed a significantly inc reased percentage of apoptosis after, growth factor withdrawal. Furthe rmore, IL-2 was more efficient than IL-15 in rescuing IL-15 expanded P HA blasts from apoptosis. In IL-15 expanded PHA blasts expression of I L-2R alpha-chain was lower than that in IL-2 expanded PHA blasts. A mo del presenting a differential role for IL-2 and IL-15 in inhibition of apoptosis in vivo is discussed.