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+ CD8hi 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+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.