HIV-1 induces primary CD34+ hematopoietic progenitors and HEL cells to release autocrine TGF-β1

We have previously demonstrated that a subset of primary peripheral blood CD34+ hemalopoietic progenitors, as well as HEL ceils express low level of CD4 antigen (up to 40%). After exposure to either heat- mac livaled HIV-1 (strain IIIB) or cross-1 inked envelope recombinant gp!20. both primary CD34+ cells and HEL continuous cell line showed an accumulation in GO/G1 and a progressive increase of apoptosis. Both effects appared to be mediated by specific inleraction(s) of envelope gpl 20 with the CD4 antigen but did not require infection of HEL or primary CD34+ cells. In blocking experiment with unti-TGF-0 1 neutralizing serum or TGF- l oligonucleotides. we found thai the HIV-1 or gpl 20 mediated suppression of CDM"" cell growth was mainly due to the upregulation of au to cri ne TGF-! produced by purified hematopoietic progenitors Ann-TGF- 1 neutralizing serum or TGF l oligonucleotides were also effective in inducing a significant increase of the plating efficiency of CÜ34+ cells, purified from the peripheral blood of three HIV-1 séropositive individuals. suggesting that a similar mechanism may be operative also in vivo. Research is in progress on HEL cell line in order to evalute whether the up-regulation ot TGF- 1 occurs at the trascripiional or post-.