A NOVEL MODE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) ACTIVATION - LIGATION OF CD28 ALONE INDUCES HIV-1 REPLICATION IN NATURALLY INFECTED LYMPHOCYTES

Induction of human immunodeficiency virus (HIV) replication in infecte d CD4+ T lymphocytes requires cellular activation. The ligation of CD2 8, a signal-transducing receptor with a natural ligand on activated B cells and antigen-presenting cells, provides a costimulating signal fo r interleukin 2 production and T-cell proliferation as well as coactiv ation of the transfected HIV long terminal repeat in Jurkat cells. The aim of the present study was to investigate the ability of CD28 ligat ion to activate HIV type 1 (HIV-1) replication in naturally infected C D4+ lymphocytes either alone or in combination with immobilized anti-C D3 monoclonal antibody. Our results show that HIV-1 was successfully i solated from 16 of 28 patients. For 5 of these 16, virus was isolated only when anti-CD28 was added in combination with the anti-CD3. Moreov er, stimulation by anti-CD28 alone induced HIV-1 replication in 5 of 1 2 patients tested, in the absence of cell proliferation. We found no c orrelation between the level of CD3- or CD28-induced proliferative res ponse and induction of HIV-1 replication. Therefore, CD28 ligation, a nonmitogenic CD4+ T-cell activation signal, is sufficient to induce tr anscription and replication of HIV-1 in naturally infected lymphocytes .