HIV-1 Nef protein expression in human CD34+ progenitors impairs the differentiation of an early T/NK cell precursor

HIV-1 impairs the production of Tcells, through mechanisms that are still unknown. Here, we investigated the effect of the expression of HIV-1 Nef on the T-cell potential of human hematopoietic CD34(+) precursors. Those progenitors were transduced by using lentiviral vectors expressing Nef and cultured on OP9-DL1 cells allowing the differentiation of T cell from human hematopoietic precursors. We demonstrate that Nef impairs the generation of a CD3 epsilon(+)CD5(+) CD1a(+) precursor stage that has initiated a D-J rearrangement of the TCR beta locus. Onward stages of T-cell development were also affected with a quantitative reduction of CD4(+) intraCD3 epsilon(+) Immature single positive cells (ISP), Double Positive (DP) CD4(+)CD8(+) TCR alpha beta Tcells and CD56(+) NK cells. But B cell production was not affected. Limiting dilution analyses demonstrated a significant reduction in the frequency of T/NK progenitors among Nef-expressing CD34(+) cells. Altogether, these data demonstrate that Nef interferes with the differentiation of a primitive lymphoid human precursor with a T/NK potential. (c) 2008 Elsevier Inc. All rights reserved.