HUMAN NEONATAL THYMIC ORGAN-CULTURE - AN EX-VIVO MODEL OF THYMOCYTE ONTOGENY AND HIV-1 INFECTION

An intact thymic microenvironment is required for the normal maturation and selection of thymocytes. This process is directed by the interaction of thymocyte progenitors with molecules on the surface of thymic stromal cells and with cytokines. The precise nature of these events is poorly understood in humans. We have developed a technique of human neonatal thymic organ culture (hNTOC) that enabled thymocyte development for up to 14 days of ex vivo culture. hNTOC supported the maturation of CD4+CD8+ double-positive cells into both CD4+CD8- and CD4-CD8+ single-positive thymocytes. hNTOC was also used to examine infection with HIV-1, as a means to address the thymic pathology of HIV-1. These results establish an experimental system for the analysis of human thymic ontogeny and for the experimental manipulation of these events by ex vivo administration of cytokines, drugs or infectious agents.