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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3513-3519. Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2004-03-0805.
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Establishment of the CD4+ T-cell pool in healthy children and untreated children infected with HIV-1From the Department of Clinical Viro-Immunology, Sanquin Research at CLB, Amsterdam, the Netherlands; the Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; the Department of Pediatrics, Sophia Children's Hospital/Erasmus University Medical Center, Rotterdam, the Netherlands; the Department of Pediatrics, Emma's Children's Hospital/Academic Medical Center, University of Amsterdam, the Netherlands; the Division of Infectious Diseases, Tropical Medicine and AIDS, the National AIDS Therapy Evaluation Center (NATEC), the Department of Internal Medicine, Academic Medical Center, University of Amsterdam, the Netherlands; the Department of Theoretical Biology, Utrecht University, the Netherlands; and the Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, the Netherlands.
Current understanding of how the T-cell pool is established in children and how this is affected by HIV infection is limited. It is widely believed that the thymus is the main source for T cells during childhood. Here we show, however, that healthy children had an age-related increase in total body numbers of naive and memory T cells, whereas absolute numbers of T-cell receptor excision circles (TRECs) did not increase. This suggests that expansion of the naive T-cell pool after birth is more dependent on T-cell proliferation than was previously recognized. Indeed, the proportion of dividing naive T cells was high, especially in younger children, which is consistent with expansion through proliferation, in addition to antigen-mediated naive T-cell activation leading to formation of the memory T-cell pool. In untreated children infected with HIV-1, total body numbers of T cells and TRECs were low and stable, whereas T-cell division levels were significantly higher than in healthy children. We postulate that in children infected with HIV, similar to adults infected with HIV, continuous activation of naive T cells leads to erosion of the naive T-cell pool and may be a major factor in lowering CD4+ T-cell numbers.
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| Copyright © 2004 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
