SELECTIVE THYMOCYTE DEPLETION IN NEONATAL HIV-1 THYMIC INFECTION

Objective: To determine the impact of HIV-1 infection on thymocyte dev elopment, and the role of thymic infection on the pathogenesis of neon atal HIV-1 infection. Design and methods: The consequences of thymic i nfection by HIV-1 were examined by comparative histologic and molecula r analyses of an asymptomatic, HIV-1-seropositive 3-day-old subject, v ersus age- and treatment-matched controls. The presence of replicating virus was established by in situ hybridization with specific molecula r probes to HIV-1. The distribution of thymocyte subsets was determine d by quantitative flow cytometry following staining with antibodies to CD4 and CD8 cell surface proteins. Results: The results show clear ev idence of severe thymic involution, HIV-1 infection of thymocytes, and selective depletion of thymocyte subpopulations. The consequences of HIV-1 infection were a marked depletion of CD3+CD4+ CD8hi and CD3+CD4CD8- cells. The phenotype of the residual thymic lymphoid population w as predominantly that of immature CD3-CD4-CD8- double negative and CD3 +CD4+CD8lo cells. Conclusion: Changes in the distribution of thymocyte subsets suggests a role for thymic involvement in the pathogenesis of HIV-1 infection in neonates.