The Anti-HIV-1 ADCC-Mediating Antibodies From Cervicovaginal Secretions of HIV-Infected Women Have an Ability to Mediate Lysing of Autologous CD4+ HIV-Infected Cells

Background: Fragment crystallizable region of antibody-mediated mechanism such as antibody-dependent cellular cytotoxicity (ADCC) has been identified as an important component of immune protection against HIV. We assessed whether the anti-HIV antibodies mediating ADCC from cervicovaginal lavages (CVLs) of HIV-infected women have an ability to mediate lysing of autologous CD4(+) HIV-infected cells. Methodology: The CVLs of 62 HIV-infected (37 long-term slow progressors and 25 with progressive HIV infection: progressors) and 20 HIV-uninfected Indian women with high risk of HIV acquisition were tested for the presence of ADCC-mediating antiHIV antibodies against HIV-1 C Env in a fluorometric assay. Furthermore, we tested the ability of these antibodies to mediate ADCC-dependent killing of the autologous HIV-infected CD4(+) T cells using paired peripheral blood mononuclear cells containing target and effector cells. Results: The numbers of ADCC responders were significantly higher in long-term slow progressors (34/37) as compared to the progressor group (9/25) with no significant difference in the magnitude. The magnitude of response was inversely associated with detectable CVL viral load (P < 0.003). The lysis of target cells was significantly higher in enriched IgG fraction as compared to the respective non-IgG fraction. The ADCC antibodies from CVLs significantly reduced the frequency of HIV-1 Env-activated autologous CD4(+) T cells in the presence of autologous effector cells. Conclusions: The presence of ADCC antibodies in CVLs with an ability to mediate lysing of HIV-infected autologous CD4(+) T cells provides evidence of their promising contribution to mucosal defense against HIV-1 and has implications in designing prophylactic and immunotherapeutic strategies.