OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+T cell depletion

Activation of resting T cells has been proposed to purge the reservoir of H IV-1-infected resting CD4+ T cells. We therefore treated three HIV-1-infect ed patients on antiretroviral therapy with OKT3, a CD3 monoclonal antibody, and recombinant human IL-2. Here we report the profound and partially long -lasting host responses induced by the OKT3 and IL-2 treatment. OKT3/IL-2 i nduced a strong but transient release of plasma cytokines and chemokines. T he percentage CD4+ and CD8+ cells in the blood expressing the activation ma rker CD38 transiently increased to almost 100%, and in lymph nodes we "obse rved" a 10-fold increase in the number of dividing Ki67+ cells and increase d numbers of apoptotic cells. Following OKT3/IL-2 treatment, a long-lasting depletion of CD4+ cells in the peripheral blood and lymph nodes occurred, suggesting the physical deletion of these cells. Increases in CD,IT cell nu mbers during the two year followup period were due mainly to increased memo ry cell numbers. CD8+ cells were also depleted in the blood, but less sever ely in lymph nodes, and returned to baseline levels within several weeks.