Selective thymocyte depletion in neonatal HIV-1 thymic infection

Objective: To determine the impact of HIV-1 infection on thymocyte development, and the role of thymic infection on the pathogenesis of neonatal HIV-1 infection. Design and methods: The consequences of thymic infection by HIV-1 were examined by comparative histologic and molecular analyses of an asymptomatic, HIV-1-seropositive 3-day-old subject, versus age- and treatment-matched controls. The presence of replicating virus was established by in situ hybridization with specific molecular probes to HIV-1. The distribution of thymocyte subsets was determined by quantitative flow cytometry following staining with antibodies to CD4 and CD8 cell surface proteins. Results: The results show clear evidence 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⁺ CD8^hi and CD3⁺CD4⁺CD8^- cells. The phenotype of the residual thymic lymphoid population was predominantly that of immature CD3^-CD4^-CD8^- double negative and CD3⁺CD4⁺CD8^lo cells. Conclusion: Changes in the distribution of thymocyte subsets suggests a role for thymic involvement in the pathogenesis of HIV-1 infection in neonates.