Establishment of the CD4+ T-cell pool in healthy children and untreated children infected with HIV-1.
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.
Department of Clinical Viro-Immunology, Sanquin Research at CLB, Amsterdam, The Netherlands.
Mette D
MD
Hazenberg
Sigrid A
SA
Otto
Annemarie M C
AM
van Rossum
Henriëtte J
HJ
Scherpbier
Ronald
R
de Groot
Taco W
TW
Kuijpers
Joep M A
JM
Lange
Dörte
D
Hamann
Rob J
RJ
de Boer
José A M
JA
Borghans
Frank
F
Miedema
D000293:Adolescent; D000367:Age Factors; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008962:Models, Theoretical