Establishment of the CD4+ T-cell pool in healthy children and untreated children infected with HIV-1

MD Hazenberg, SA Otto, AMC van Rossum… - Blood, 2004 - ashpublications.org
MD Hazenberg, SA Otto, AMC van Rossum, HJ Scherpbier, R de Groot, TW Kuijpers…
Blood, 2004ashpublications.org
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 …
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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