HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GLYCOPROTEIN 120-SPECIFIC T-LYMPHOCYTES PROVIDE INTERMOLECULAR HELP FOR ANTI-CD4 AUTOANTIBODY PRODUCTION IN EXPOSED UNINFECTED SUBJECTS

Anti-CD4 antibodies have been documented in about 10-20% of HIV-infect ed patients, This autoimmune response could be triggered by increased CD4 processing and unveiling of hidden (cryptic) epitopes, Multiple ma rkers of exposure to HIV have been described in exposed uninfected ind ividuals, Here, we investigated the mechanisms underlying the generati on of anti-CD4 antibodies in a cohort of 54 seronegative exposed uninf ected individuals, We identified anti-CD4 antibodies above normal leve ls in 16 of 47 (34%) exposed uninfected subjects, The fine specificity of these antibodies was different in this cohort when compared with t hose found in HIV+ patients, This suggested the possibility of differe nt mechanisms underlying the generation of anti-CD4 antibodies in thes e two groups. Indeed, in exposed uninfected subjects, we found circula ting CD4 T cells specific for gp120, but not for CD4. In contrast, HIV -l-seropositive patients had peripheral blood T cells specific for bot h molecules, Noncovalent binding of gp120 to soluble CD4 enhanced acti vation of gp120-specific T lymphocytes in exposed uninfected subjects, but not in HIV+ subjects, Moreover, gp120-specific T cells isolated f rom exposed uninfected, but not from HIV+, subjects provided help for anti-CD4 antibody production by B cells pulsed with CD4-gp120 complex, We conclude that gp120-specific T cells are present in exposed uninfe cted individuals, and can provide intermolecular help for anti-CD4 ant ibody production, This mechanism is distinct from that found in HIV-l- seropositive patients and may play a protective role against HIV-1 inf ection in vivo.