2 SUBPOPULATIONS OF HUMAN TRIPLE-NEGATIVE THYMIC CELLS ARE SUSCEPTIBLE TO INFECTION BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN-VITRO

Some infants infected with human immunodeficiency virus type 1 (HIV-1) rapidly develop a fatal disease characterized by a severe lymphopenia . To explain the immune dysfunction, we proposed a mechanism by which a nongeneration of CD4(+) T cells is caused by HIV-1 infection of thym ic cells. To examine this hypothesis, we infected primary triple-negat ive (TN; phenotypically CD3(-) CD4(-) CD8(-)), CD1a(-) TN, or CD1a(+) TN thymic cell subsets. Our data indicate that by flow cytometry, TN, CD1a(-) TN, and CD1a(+) TN cells remain CD4 negative throughout the cu lture period. We demonstrated that TN and CD1a(+) TN thymic cell subse ts are susceptible to HIV-1 as is the entire thymic cell population, w hereas CD1a(-) TN cells are not. A limited number of infected TN cells are expressing HIV-1 but the level of transcription is very high in p ermissive cells, as detected by in situ hybridization. We then perform ed blocking experiments on TN cells to examine the mechanism of HIV-1 entry into these cells. CD4 (OKT4a) monoclonal antibody blocks their i nfection. Finally, infection experiments on two subpopulations of TN c ells (CD2(+) CD7(+) and CD2(-) CD7(-)) indicate that infected TN cells may correspond to both immature thymocytes and thymic dendritic cells . These data are of particular interest since infection of thymic stro mal cells might result in an impairment of T-cell differentiation, whi ch may explain a nongeneration of functional CD4(+). T-cell population in the thymus. This phenomenon may play a role in AIDS pathogenesis, in particular in infants born from seropositive mothers.