Yin Li, Rodriguez Carina A, Hou Wei, Potter Olivia, Caplan Margaret J, Goodenow Maureen M, Sleasman John W
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Fla, USA.
J Allergy Clin Immunol. 2008 Jul;122(1):166-72, 172.e1-2. doi: 10.1016/j.jaci.2008.04.029. Epub 2008 Jun 9.
HIV infection decreases thymic output and induces chronic T-cell activation.
To examine the reconstitution of naive and activated T cells.
Extended immune phenotyping of CD4(+) and CD8(+) T-cell subsets was combined with T-cell receptor rearrangement excision circle (TREC) levels and measures of T-cell receptor repertoire perturbations in CD8(+) T-cell subpopulation to define the global effect of HIV-1 on T-cell dynamics. Evaluations before and after therapy were performed in HIV-infected children and compared with those in healthy individuals.
Ten HIV-infected children and adolescents with a broad range of pretherapy CD4(+) T-cell counts were compared with healthy individuals. Pretherapy late activated CD8(+) T cells (CD3(+)CD8(+)CD45RA(+)CD27(-)CD11a(bright) cells) were expanded among HIV-infected subjects. Successful antiretroviral therapy increased the proportion of naive T cells (CD3(+)CD4(+)CD45RA(+)CD27(+)CD28(+) and CD3(+)CD8(+)CD45RA(+)CD27(+)CD11a(dim) cells), with a significant decrease in late activated CD8(+) T cells. The proportion of naive CD4(+) and CD8(+) T cells significantly predicted log(10) TREC copies/10(6) PBMCs in infected children and healthy control subjects, with a negative correlation in late activated CD8(+) T cells and activated CD4(+) T cells. Treatment re-established Gaussian distributions and decreased oligoclonal expansion within the Vbeta repertoire of CD8(+)CD45RA(+) T cells, but compared with that seen in healthy children, the proportion of late activated CD8(+) T cells remained increased.
HIV infection strikingly shifts the proportion of naive and late activated CD45RA(+)CD8(+) T cells. Homeostasis within this T-cell population reflects TREC levels and the extent of T-cell receptor Vbeta perturbations.
HIV感染会降低胸腺输出并诱导慢性T细胞活化。
研究初始T细胞和活化T细胞的重建情况。
对CD4(+)和CD8(+) T细胞亚群进行扩展免疫表型分析，并结合T细胞受体重排切除环（TREC）水平以及CD8(+) T细胞亚群中T细胞受体库扰动的测量，以确定HIV-1对T细胞动力学的整体影响。在HIV感染儿童治疗前后进行评估，并与健康个体进行比较。
将10名HIV感染儿童和青少年（治疗前CD4(+) T细胞计数范围广泛）与健康个体进行比较。在HIV感染受试者中，治疗前晚期活化的CD8(+) T细胞（CD3(+)CD8(+)CD45RA(+)CD27(-)CD11a(bright)细胞）有所增加。成功的抗逆转录病毒治疗增加了初始T细胞（CD3(+)CD4(+)CD45RA(+)CD27(+)CD28(+)和CD3(+)CD8(+)CD45RA(+)CD27(+)CD11a(dim)细胞）的比例，晚期活化的CD8(+) T细胞显著减少。在感染儿童和健康对照受试者中，初始CD4(+)和CD8(+) T细胞的比例显著预测了log(10) TREC拷贝数/10(6)外周血单核细胞（PBMC），晚期活化的CD8(+) T细胞和活化的CD4(+) T细胞呈负相关。治疗重新建立了高斯分布，并减少了CD8(+)CD45RA(+) T细胞Vβ库内的寡克隆扩增，但与健康儿童相比，晚期活化的CD8(+) T细胞比例仍有所增加。
HIV感染显著改变了初始和晚期活化的CD45RA(+)CD8(+) T细胞的比例。该T细胞群体的稳态反映了TREC水平和T细胞受体Vβ扰动的程度。
