Human immunodeficiency virus nef gene expression affects generation and function of human T cells, but not dendritic cells

Human immunodeficiency virus (HIV)-infected individuals develop an acquired immune deficiency syndrome (AIDS) due to loss in their lymphocyte numbers and cellular defects in T cells and antigen-presenting cells (APC), HIV inf ection of the thymus results in deficient replenishment of the peripheral n aive T-cell pool, The HIV nef gene was shown to be important for progressio n towards AIDS and cellular depletion of the infected thymus, Here, we demo nstrate by retroviral gene transfer that nef expression, in the absence of other HIV genes, impaired human thymic T-cell development, Thymocytes were generated in reduced numbers and downmodulated CD4 and CD8 beta cell surfac e expression, T cells grown from nef-expressing thymocytes were hyperprolif erative in vitro upon T-cell receptor triggering, Mature dendritic cells (D C) were functional and had normal surface CD4 levels despite nef expression . Thus, nef expression alone may contribute to AIDS development by reduced T-cell generation and T-cell hyperresponsiveness. (C) 1999 by The American Society of Hematology.