急性猴免疫缺陷病毒感染期间的T细胞动态变化。
T-cell dynamics during acute SIV infection.
作者信息
Mattapallil Joseph J, Letvin Norman L, Roederer Mario
机构信息
Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20895, USA.
出版信息
AIDS. 2004 Jan 2;18(1):13-23. doi: 10.1097/00002030-200401020-00002.
OBJECTIVES
To delineate T-cell dynamics during acute SIV infection, particularly of phenotypically defined memory T cell subsets.
DESIGN
T cells are a heterogeneous mix of naive and memory subsets delineated by simultaneously measuring CD4, CD8, CD45RA/RO, CD11a, CD28, and CD27. The effects of SIV infection on these subsets was measured to evaluate the impact of changes in functionally distinct cell types during pathogenesis.
METHODS
Peripheral blood was obtained from six SIV-infected macaques at multiple times before and after SIV infection and analyzed using 12-color flow cytometry.
RESULTS
Acute infection was characterized by an initial lymphopenia caused by a decline in B cells. Total T-cell counts remained steady during the early acute phase; however, CD4 cell counts declined while CD8 T cells increased. The decline in CD4 T cells was a result of a decline in both naive and memory cells. CCR5+ or CD103+ subsets of CD4 T cells were depleted but only partially accounted for the decline of CD4 memory T cells, suggesting that acute infection was associated with a rapid redistribution of T cells from the periphery. Naive CD8 cell counts declined while memory CD8 cell counts increased. The increase coincided with declines in plasma viremia and was made up initially of CD27-CD28- (effector) cells; subsequently, the predominant phenotype became CD27+CD28-, akin to central memory cells.
CONCLUSIONS
A complete understanding of the T-cell dynamics during acute SIV or HIV infection requires the simultaneous evaluation of a broad spectrum of T-cell subsets. Changes in homeostasis and associated immunopathogenesis can no longer be accurately described simply by measuring naive and memory T-cell subsets.
目的
描绘急性猴免疫缺陷病毒(SIV)感染期间的T细胞动态变化,尤其是表型定义的记忆T细胞亚群的动态变化。
设计
T细胞是由幼稚细胞和记忆亚群组成的异质性混合群体,可通过同时检测CD4、CD8、CD45RA/RO、CD11a、CD28和CD27来进行区分。测量SIV感染对这些亚群的影响,以评估发病过程中功能不同的细胞类型变化所产生的影响。
方法
在SIV感染前后的多个时间点,从6只感染SIV的猕猴获取外周血,并使用12色流式细胞术进行分析。
结果
急性感染的特征是最初由B细胞减少导致的淋巴细胞减少。在急性早期,总T细胞计数保持稳定;然而,CD4细胞计数下降,而CD8 T细胞增加。CD4 T细胞的减少是幼稚细胞和记忆细胞均减少的结果。CD4 T细胞的CCR5+或CD103+亚群减少,但仅部分解释了CD4记忆T细胞的减少,这表明急性感染与T细胞从外周的快速重新分布有关。幼稚CD8细胞计数下降,而记忆CD8细胞计数增加。这种增加与血浆病毒血症的下降同时发生,最初由CD27-CD28-(效应)细胞组成;随后,主要表型变为CD27+CD28-,类似于中央记忆细胞。
结论
要全面了解急性SIV或HIV感染期间的T细胞动态变化,需要同时评估广泛的T细胞亚群。仅通过测量幼稚和记忆T细胞亚群,已无法准确描述稳态变化及相关的免疫发病机制。