CD4+ memory T cells are the predominant population of HIV-1-infected lymphocytes in neonates and children.
BACKGROUND: CD4+ memory T cells express CD45RO and are the principal viral reservoir in HIV-infected adults. In infants and children, CD45RO T cells comprise the minority of the CD4+ T-cell population. The majority of blood CD4+ T cells are naive, expressing CD45RA. OBJECTIVE: To determine the developmental stage at which pediatric CD4+ T cells become susceptible to HIV-1 infection in vivo by determining which T-cell population harbors HIV-1 proviral DNA. DESIGN: A prospective, cross-sectional analysis of peripheral blood CD8+ T cells, CD45RA, or CD45RO CD4+ T cells obtained from 10 HIV-infected neonates and children were analysed for provirus. METHODS: Semi-quantitative polymerase chain reaction methods were used to detect HIV-1 proviral DNA within purified lymphocyte populations selected using immunoaffinity magnetic microspheres. RESULTS: CD8+ T cells harbored no detectable HIV-1, indicating that infection of common thymocytes does not contribute to the population of infected blood T cells. In five children and two of the five neonates, the CD4+ CD45RO memory T lymphocytes contained 10-100-fold greater numbers of infected cells than the CD4+ CD45RA naive T-cell population. Three neonates, who exhibited rapid disease progression, demonstrated high proviral levels in their CD4+ CD45RA T cells. The normal age-related predominance of CD4+ CD45RA T cells was preserved independent of CD4+ T-cell attrition. CONCLUSIONS: The majority of HIV-1-infected blood CD4+ T cells in infants and children are restricted to the small population of terminally differentiated CD4+ CD45RO memory T cells. Neonates with rapid CD4+ T-cell attrition display high levels of provirus in their CD4+ CD45RA T-cell population.
Sleasman, JW; Aleixo, LF; Morton, A; Skoda-Smith, S; Goodenow, MM
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