Hazenberg Mette D, Otto Sigrid A, van Rossum Annemarie M C, Scherpbier Henriëtte J, de Groot Ronald, Kuijpers Taco W, Lange Joep M A, Hamann Dörte, de Boer Rob J, Borghans José A M, Miedema Frank
Department of Clinical Viro-Immunology, Sanquin Research at CLB, Amsterdam, The Netherlands.
Blood. 2004 Dec 1;104(12):3513-9. doi: 10.1182/blood-2004-03-0805. Epub 2004 Aug 5.
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.
目前对于儿童T细胞库如何建立以及HIV感染如何影响这一过程的理解有限。人们普遍认为胸腺是儿童期T细胞的主要来源。然而,我们在此表明,健康儿童体内幼稚和记忆T细胞的总数随年龄增长而增加,而T细胞受体切除环(TRECs)的绝对数量并未增加。这表明出生后幼稚T细胞库的扩增比之前认为的更依赖于T细胞增殖。事实上,正在分裂的幼稚T细胞比例很高,尤其是在年幼的儿童中,这与通过增殖进行扩增一致,此外抗原介导的幼稚T细胞活化会导致记忆T细胞库的形成。在未经治疗的HIV - 1感染儿童中,T细胞总数和TRECs较低且稳定,而T细胞分裂水平显著高于健康儿童。我们推测,与HIV感染的成年人一样,HIV感染儿童体内幼稚T细胞的持续活化会导致幼稚T细胞库的损耗,这可能是CD4(+) T细胞数量降低的主要因素。