Productive infection of neonatal CD8+ T lymphocytes by HIV-1

CD8(+) T lymphocytes confer significant but ultimately insufficient protection against HIV infection. Here were report that activated neonatal CD8(+) T cells can be productively infected in vitro by macrophage-tropic (M-tropic) HIV-1 isolates, which are responsible for disease transmission, whearas they are resistant to T cell-tropic (T-tropic) HIV strains. Physiological activation of CD8-alpha/beta(+) CD4(-) cell receptor-alpha/beta(+) neonatal T cells, including activation by allogeneic dendritic cells, induces the accumulation of CD4 messenger RNA and the expression of CD4 Ag on the cell surface. The large majority of anti-CD3/B7.1-activated cord blood CD8(+) T cells coexpress CD4. the primary HIV receptor, as well as CCR5 and CXCR4, the coreceptors used by M- and T-tropic HIV-1 strains, respectively, to enter target cells. These findings are relevant to the rapid progression of neonatal HIV infection. Infection of primary HIV-specific CD8(+) T cells may compromise their survival and thus significantly contribute to the failure of the immune system to control the infection. Furthermore, these results indicate a previously unsuspected level of plasticity in the neonatal immune system in the regulation of CD4 expression by costimulation.