Neonatal HIV-1 thymic infection.

The thymus is the primary site of T cell ontogeny and selection during fetal and neonatal development. Previous studies have established that the thymus is also a site of HIV-1 infection, as early as the first trimester of pregnancy. Alteration of the thymocyte maturation process by HIV-1 could impact on the peripheral T cell population and interfere with immune responses. A neonatal thymic organ culture system was established to study HIV-1 infection within the thymus. We have shown that this primary tissue isolate can support a productive HIV-1 infection. Infection occurred without detectable thymocyte cytopathology. The ability to infect the developing thymocyte within an intact micro environment will enable us to further establish the kinetics of acute HIV-1 thymic infection and its consequences on lymphocyte maturation.

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.