Resting CD4⁺ T cells with CD38⁺CD62L⁺ produce interleukin-4 which contributes to enhanced replication of T-tropic human immunodeficiency virus type 1

A significant increase in the CD38⁺ population among T lymphocytes has been observed in human immunodeficiency virus type 1 (HIV-1)-infected carriers. We previously reported a higher replication rate of T-tropic HIV-1 in the CD4⁺CD38⁺CD62L⁺ than CD38^- subset under conditions of mitogen stimulation after infection. Here, we revealed a similarly high susceptibility in the CD38⁺ subset on culture with conditioned medium containing Th2 cytokine, interleukin (IL)-4 that was produced endogenously from this subset on stimulation with mitogen or anti-CD3 antibody for 3 days. The contribution of IL-4 to the upregulated production of virus in the CD38⁺ subset was confirmed by culture of this subset with recombinant human IL-4. In contrast, the rate of replication in the CD38^- subset was not augmented in the conditioned medium from either subset or with IL-4. However, there were no differences in the surface expression of IL-4 receptor or HIV-1 receptors CD4 and CXCR4 between the two subsets. Thus, the CD4⁺CD38⁺CD62L⁺ subset comprises a specific cell population secreting endogenous Th2 cytokine that contributes to the efficient production of T-tropic HIV-1 through upregulation at a certain stage of the viral life cycle, probably after the adsorption step.