The skin as target, vector, and effector organ in human immunodeficiency virus disease

Langerhans cells are CD4+ antigen-presenting cells in the dendritic cell family that can initiate primary and secondary immune responses after emigration from skin and mucosa. Because of these properties, Langerhans cells have been proposed as potential targets for human immunodeficiency virus (HIV) infection and as potential vectors for the transmission of primary HIV infection to T cells after mucosal exposure. In support of this theory, previous investigative studies have demonstrated that Langerhans cells are targets for HIV infection both in vivo and in vitro and that HIV-pulsed Langerhans cells, as well as blood dendritic cells, induce a productive infection in co-cultured T cells in vitro. In addition, Langerhans cell dysfunction has been proposed as contributing to the pathogenesis of some of the cutaneous manifestations observed in HIV+ individuals. In a recent study, we detected Langerhans cell dysfunction in patients with acquired immune deficiency syndrome, but not in earlier stages of HIV disease. Here we review previous and current investigative studies on HIV and the skin, with an emphasis on Langerhans cells, and discuss possible future investigations in this field.