Productive infection of neonatal CD8+ T lymphocytes by HIV-1.
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.
Yang
L P
LP
University of Montreal, Centre de Recherche Louis-Charles Simard, Hôpital Notre-Dame, Montreal, Quebec H2L 4M1, Canada.
Riley
J L
JL
Carroll
R G
RG
June
C H
CH
Hoxie
J
J
Patterson
B K
BK
Ohshima
Y
Y
Hodes
R J
RJ
Delespesse
G
G
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
D015704:CD4 Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015728:Receptors, HIV