title: IL-12 inhibits apoptosis induced in a human Th1 clone by gp120/CD4 cross-linking and CD3/TCR activation or by IL-2 deprivation.
abstract: 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 CD4 cross-linking, obtained either by mouse anti-CD4 mAb plus goat anti-mouse or by recombinant gp120 plus anti-gp120 mAb, followed by activation with immobilized anti-CD3 or anti-TCR mAb, induced apoptosis at early times (15-25% apoptotic cells at 4 hr), whereas IL-2 deprivation required longer times (20-40 hr) to induce apoptosis. Both CD4 cross-linking and IL-2 deprivation-induced apoptosis appeared to be PTK-dependent 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 Th1 lymphocytes and that IL-2 and IL-12 could be used to prevent this phenomenon.
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Radrizzani
authors.forename: P
authors.initials: P
authors.lastname: Accornero
authors.forename: A
authors.initials: A
authors.lastname: Amidei
authors.forename: A
authors.initials: A
authors.lastname: Aiello
authors.forename: D
authors.initials: D
authors.lastname: Delia
authors.forename: R
authors.initials: R
authors.lastname: Kurrle
authors.forename: M P
authors.initials: MP
authors.lastname: Colombo
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D017252:CD3 Complex; D015704:CD4 Antigens; D002999:Clone Cells; D003432:Cross-Linking Reagents; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000172:deficiency*; D011948:Receptors, Antigen, T-Cell; D018417:Th1 Cells / Q000187:drug effects*
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D003432:Cross-Linking Reagents; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12