IL-12 INHIBITS APOPTOSIS INDUCED IN A HUMAN TH1 CLONE BY GP120 CD4 CROSS-LINKING AND CD3/TCR ACTIVATION OR BY IL-2 DEPRIVATION/

The aim of our work was to study apoptosis as a possible mechanism of CD4(+) lymphocyte depletion in AIDS patients and to test whether IL-12 could limit this phenomenon. As an in vitro model, we used a human IL -2-dependent Th1 clone from an uninfected individual. We found that CD 4 cross-linking, obtained either by mouse anti-CD4 mAb plus goat anti- mouse or by recombinant gp120 plus anti-gp120 mAb, followed by activat ion with immobilized anti-CD3 or anti-TCR mAb, induced apoptosis at ea rly times (15-25% apoptotic cells at 4 hr), whereas IL-2 deprivation r equired longer times (20-40 hr) to induce apoptosis. Both CD4 cross-li nking and IL-2 deprivation-induced apoptosis appeared to be PTK-depend ent and were inhibited by either IL-2 or IL-12. Our data suggest that in vivo CD4/gp120 interactions could directly prime the apoptosis of T h1 lymphocytes and that IL-2 and IL-12 could be used to prevent this p henomenon. (C) 1995 Academic Press, Inc.