Mechanism of γδ T-Cell-Mediated Inhibition of Stem Cell Differentiationin Vitro:Possible Relevance for Myelosuppression in HIV-Infected Individuals

We investigated whether γδ T cells contribute to the suppression of myelopoiesis in HIV infection. Freshly isolated γδ T cells from HIV seropositive patients suppressed CFU–GM growthin vitro.Preactivation of γδ T cells with IL-2 and/or IL-15 further reduced the number of CFU–GM. Natural killer cells and to a lower extent CD4+and CD8+cells also inhibited CFU–GM growth. In contrast to γδ T cells, this effect was not dependent on IL-15 or IL-2 preactivation. Moreover, no enhanced inhibitory effect of CD56+and CD4+cells was observed in HIV+subjects compared to HIV−donors. The myelosuppressive effect of supernatants of γδ T cells could be inhibited by antibodies against IFN-γ or TNF-α. Accordingly, we found increased numbers of TNF-α- or IFN-γ-secreting CD8+γδ T cells in HIV+patients. We conclude that the increased fraction of activated γδ T cells producing myelosuppressive cytokines might contribute to the dyshematopoiesis frequently observed in HIV-infected individuals.