Three memory subsets of human CD8+ T cells differently expressing three cytolytic effector molecules
Three memory subsets of human CD8+ T cells differently expressing three cytolytic effector molecules
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DOI：
10.4049/jimmunol.177.7.4330
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Takiguchi, Masafumi
中科院分区：
文献类型：
--
作者：
Takata, Hiroshi;Takiguchi, Masafumi
多色流式细胞术分析三种效应分子的表达，即，人CD 8（+）T细胞中的穿孔素（Per）、颗粒酶A（GraA）和颗粒酶B（GraB）的表达表明，它们包括5个亚群，这意味着CD 8（+）T细胞的分化途径如下：Per（-）GraA（-）GraB（-）-> Per（-）GraA（+）GraB（-）-> Per（低）GraA（+）GraB（-）-> Per（低）GraA（+）GraB（+）-> Per（高）GraA（+）GraB（+）。通过结合CCR 7和CD 45 RA的表达或CD 27、CD 28和CD 45 RA的表达对这些分子在亚群中的表达进行分析，表明功能性CD 8（+）T细胞亚群可以通过这些表型分类部分鉴定。然而，通过使用五种细胞表面标记物或三种细胞表面标记物和三种细胞溶解分子的分类，可以精确地鉴定功能亚群。Per（-）GraA（-）GraB（-）和Per（-/低）GraA（+）GraB（-）细胞主要见于CCR 5（-）CCR 7（+）和CCR 5（-）中。表达CD 27（+）CD 28（+）CD 45 RA（-）表型的CD 8（+）T细胞的CCR 7（-）（高/低）亚群，而Per（低）GraA（+）GraB（+）细胞存在于表达该表型的那些细胞的CCR 5（低）CCR 7（-）亚群和表达CD 27（-/低）CCR 7（-）亚群的一部分中。低）CD 28（-）CD 45 RA（-/+）表型。作为Per（低/-）GraA（+）GraB（-/+）细胞的离体EBV特异性CD 8（+）T细胞几乎不杀死靶细胞或杀死靶细胞非常弱，表明这些不是效应T细胞。这些发现表明Per（-）GraA（-）GraB（-）、Per（-/低）GraA（+）GraB（-）和Per（低）GraA（+）GraB（+）细胞分别是中央记忆、早期效应记忆和晚期效应记忆T细胞。Per（-/低）GraA（+）GraB（-）细胞在TCR刺激后获得GraB表达，表明早期效应记忆T细胞可以分化为晚期效应T细胞和效应T细胞。本研究显示了三个记忆亚群的存在及其分化途径。
Multicolor flow cytometric analysis for the expression of three effector molecules, i.e., perforin (Per), granzyme A (GraA), and granzyme B (GraB), in human CD8(+) T cells demonstrated that they included five subpopulations, implying the following pathway for the differentiation of CD8(+) T cells: Per(-)GraA(-)GraB(-)-> Per(-)GraA(+)GraB(-)-> Per(low)GraA(+)GraB(-)-> Per(low)GraA(+)GraB(+)-> Per(high)GraA(+)GraB(+). The analysis of the expression of these molecules in the subsets classified by the combination of the expression of CCR7 and CD45RA or by that of CD27, CD28, and CD45RA showed that functional CD8(+) T cell subsets could be partially identified by these phenotypic classifications. However, the functional subsets could be precisely identified by the classification using five cell surface markers or three cell surface markers and three cytolytic molecules. Per(-)GraA(-)GraB(-) and Per(-/low)GraA(+)GraB(-) cells were predominantly found in CCR5(-)CCR7(+) and CCR5(high/low)CCR7(-) subsets, respectively, of CD8(+) T cells expressing the CD27(+)CD28(+)CD45RA(-) phenotype, whereas Per(low)GraA(+)GraB(+) cells were found in the CCR5(low)CCR7(-) subset of those expressing this phenotype and in a part of the CCR5(-/low)CCR7(-) subset of those expressing the CD27(-/low)CD28(-)CD45RA(-/+) phenotype. Ex vivo EBV-specific CD8(+) T cells, which were Per(low/-)GraA(+)GraB(-/+) cells, hardly or very weakly killed the target cells, indicating that these were not effector T cells. These findings suggest that the Per(-)GraA(-)GraB(-), Per(-/low)GraA(+)GraB(-), and Per(low)GraA(+)GraB(+) cells were central memory, early effector memory, and late effector memory T cells, respectively. Per(-/low)GraA(+)GraB(-) cells gained GraB expression after TCR stimulation, indicating that early effector memory T cells could differentiate into late effector and effector T cells. The present study showed the existence of three memory subsets and the pathway for their differentiation.