GENERATION OF HUMAN T-LYMPHOCYTES FROM BONE-MARROW CD34(-VITRO() CELLS IN)

Analysis of the events that regulate development of red blood cells or granulocytes has led to therapies altering clinical conditions associ ated with anemia or neutropenia. The development of therapeutic approa ches to target conditions associated with lymphopenia, such as AIDS, h as been thwarted by limited techniques for studying T-lymphocyte devel opment. We describe an in vitro system in which human bone marrow CD34 cells proliferate, acquire the expression of the lymphoid-specific RA G-2 gene and a broad repertoire of rearranged T-cell receptor genes, d evelop the ability to produce T cell-specific interleukin-2 and achiev e a range of T-cell immunophenotypes. The cells also become susceptibl e to infection with the T-lymphotropic strain of human immunodeficienc y virus-1, HIV-1(IIB). This culture system induces human T lymphopoies is and may permit further analysis of the events regulating human T-li neage differentiation. It provides a preclinical model for screening s tem cell gene therapies directed toward AIDS.