title: Productive infection of neonatal CD8+ T lymphocytes by HIV-1.
abstract: CD8+ T lymphocytes confer significant but ultimately insufficient protection against HIV infection. Here we 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, whereas they are resistant to T cell-tropic (T-tropic) HIV strains. Physiological activation of CD8-alpha/beta+ CD4- T 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.
authors.affiliation: University of Montreal, Centre de Recherche Louis-Charles Simard, Hôpital Notre-Dame, Montreal, Quebec H2L 4M1, Canada.
authors.forename: L P
authors.initials: LP
authors.lastname: Yang
authors.forename: J L
authors.initials: JL
authors.lastname: Riley
authors.forename: R G
authors.initials: RG
authors.lastname: Carroll
authors.forename: C H
authors.initials: CH
authors.lastname: June
authors.forename: J
authors.initials: J
authors.lastname: Hoxie
authors.forename: B K
authors.initials: BK
authors.lastname: Patterson
authors.forename: Y
authors.initials: Y
authors.lastname: Ohshima
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodes
authors.forename: G
authors.initials: G
authors.lastname: Delespesse
mesh_terms: D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007231:Infant, Newborn; D008264:Macrophages / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015728:Receptors, HIV