HIV type 1-specific IgG2 antibodies: Markers of helper T cell type 1 response and prognostic marker of long-term nonprogression

The helper T type 1 (Th1) function of CD4(+) T lymphocytes is presumed to b e of key importance in host defense against HIV-1. As the production of dif ferent antibody isotypes is dependent on this helper T function, we investi gated whether HIV-1-specific responses of a particular IgG isotype could be a reliable marker of long-term HIV-1 control. Assessment of the IgG subcla ss distribution in the plasma of HIV-1-infected patients enrolled in the Fr ench prospective Asymptomatic Long-Term (ALT) cohort showed that IgG2 direc ted against HIV-1 Env gp41 and Gag proteins was associated with low viral l oad, high CD4(+) lymphocyte count, and weak neutralizing activity. By contr ast, levels of anti-Env and anti-Pol IgG1 as well as the magnitude of neutr alizing activity were correlated with the viral load and thus merely reflec t the level of HIV replication. Furthermore, IgG2 directed against Gag prot eins was significantly associated with HIV-1 p24-specific Th1 cell producti on of interferon gamma and interleukin 2. In multivariate analysis, only tw o variables, anti-gp41 IgG2 and plasma HIV-1 RNA, were found to be independ ent prognostic factors of remaining long-term nonprogressive over time. By providing new insight into the nature of an HIV-specific antibody response associated with the control of virus replication, these findings have impli cations for the design of HIV vaccines.