Immune activation set point during early FHV infection predicts subsequent CD4+ T-cell changes independent of viral load
Immune activation set point during early FHV infection predicts subsequent CD4+ T-cell changes independent of viral load
复制标题
DOI：
10.1182/blood-2003-09-3333
复制
发表时间：
2004-08-15
期刊：
影响因子：
20.3
通讯作者：
Hecht, FM
中科院分区：
文献类型：
--
作者：
Deeks, SG;Kitchen, CMR;Hecht, FM
尽管全身性t细胞活化是慢性HIV发病机制中的一个重要因素，但其在原发性感染中的作用仍不明确。为了研究免疫激活对早期HIV感染受试者t细胞变化的影响，并验证免疫激活“设定点”在HIV疾病自然史早期建立的假设，对急性感染成人进行了前瞻性队列研究。在68例抗逆转录病毒治疗组和83例抗逆转录病毒治疗组中，纵向测量CD4（+）和CD8(+) T细胞上CD38分子的中位密度。在研究开始时，t细胞激活与病毒血症呈正相关，当血浆HIV RNA水平超过10,000拷贝/mL时，CD8(+) t细胞激活水平呈指数增长。在未经治疗的患者中，CD8(+) t细胞活化水平在个体之间差异很大，但在给定个体内通常保持稳定。随着时间的推移，CD8(+) t细胞活化和血浆HIV RNA水平与未治疗个体的CD4(+) t细胞损失率独立相关。这些数据表明，免疫激活设定点在HIV感染早期就建立起来了，这个设定点决定了CD4(+) T细胞随时间流失的速度。(C) 2004年由美国血液病学会出版。
Although generalized T-cell activation is an important factor in chronic HIV disease pathogenesis, its role in primary infection remains poorly defined. To investigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunologic activation "set point" is established early in the natural history of HIV disease, a prospective cohort of acutely infected adults was performed. The median density of CD38 molecules on CD4(+) and CD8(+) T cells was measured longitudinally in 68 anti retrovi ral-u ntreated individuals and 83 antiretroviraltreated individuals. At study entry, T-cell activation was positively associated with viremia, with CD8(+) T-cell activation levels increasing exponentially at plasma HIV RNA levels more than 10 000 copies/mL. Among untreated patients, the level of CD8(+) T-cell activation varied widely among individuals but often remained stable within a given individual. CD8(+) T-cell activation and plasma HIV RNA levels over time were independently associated with the rate of CD4(+) T-cell loss in untreated individuals. These data indicate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4(+) T cells are lost over time. (C) 2004 by The American Society of Hematology.