HIV-1-induced thymocyte depletion is associated with indirect cytopathicity and infection of progenitor cells in vivo

Direct and indirect cytopathic mechanisms have been proposed to account for the loss of CD4 + T cells after infection with human immunodeficiency virus type 1 (HIV-1). We report here that HIV-1 infection of the human thymus in vivo results in thymocyte depletion by at least two different mechanisms. Thymocytes within multiple stages of differentiation are induced to die of apoptosis; most of these cells are uninfected. Additionally, thymopoiesis is interrupted by direct infection and destruction of intrathymic CD3 −CD4 +CD8 − progenitor cells. These mechanisms are differentially induced by distinct isolates of HIV-1.