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, Frank Miedema

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Abstract

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. (C) 2004 by The American Society of Hematology
Original languageEnglish
Pages (from-to)3513-3519
JournalBlood
Volume104
Issue number12
DOIs
Publication statusPublished - 2004

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