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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.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Establishment of the CD4+ T-cell pool in healthy children and untreated children infected with HIV-1
Mette D. Hazenberg,
Sigrid A. Otto,
Annemarie M.C. van Rossum,
Henriëtte J. Scherpbier,
Ronald de Groot,
Taco W. Kuijpers,
Joep M.A. Lange,
Dörte Hamann,
Rob J. de Boer,
José A.M. Borghans, and
Frank Miedema
From 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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