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

We investigated whether gamma delta T cells contribute to the suppression of myelopoiesis in HlV infection. Freshly isolated gamma delta T cells from HIV seropositive patients suppressed CFU-GM growth in vitro. Preactivation of gamma delta 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 gamma delta 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 gamma delta T cells could be inhibited by antibodies against IFN-gamma or TNF-alpha. Accordingly, we found increased numbers of IFN-gamma or TNF-alpha secreting CD8(+) gamma delta T cells in HIV+ patients. We conclude that the increased fraction of activated gamma delta T cells producing myelosuppressive cytokines might contribute to the dyshematopoiesis frequently observed in HIV-infected individuals. (C) 1998 Academic Press.