Phenotypic and functional separation of memory and effector human CD8+ T cells.

Phenotypic and functional separation of memory and effector human CD8+ T cells.
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DOI:
10.1084/jem.186.9.1407
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发表时间:
1997-11-03
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
van Lier RA
van Lier RA
中科院分区:
其他
文献类型:
--
作者:
Hamann D;Baars PA;Rep MH;Hooibrink B;Kerkhof-Garde SR;Klein MR;van Lier RA

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人类 CD8+ 记忆型和效应型 T 细胞的定义不明确。我们在此表明​​,在原始隔室旁边,可以在循环的人类 CD8+ T 细胞亚群中发现两个离散的引发亚群。首先,CD45RA−CD45R0+ 细胞让人想起记忆型 T 细胞,因为与初始 CD8+ T 细胞相比,它们表达升高水平的 CD95 (Fas) 和整合素家族成员 CD11a、CD18、CD29、CD49d 和 CD49e,并且不仅能够分泌白细胞介素 (IL) 2,还能够分泌干扰素 γ、肿瘤坏死因子 α 和 IL-4。该子集在没有事先体外刺激的情况下不会发挥细胞溶解活性,但含有病毒特异性细胞毒性 T 淋巴细胞 (CTL) 前体。第二引发群体的特征在于CD45RA表达,同时缺乏共刺激分子CD27和CD28的表达。 CD8+CD45RA+CD27− 群体包含表达高水平 CD11a、CD11b、CD18 和 CD49d 的 T 细胞,而 CD62L(L-选择素)不表达。这些T细胞不分泌IL-2或-4,但可以产生IFN-γ和TNF-α。根据这一发现,该亚群中包含的细胞的增殖依赖于外源生长因子,例如IL-2和-15。有趣的是,CD8+CD45RA+CD27−细胞平行的效应CTL,因为它们大量表达Fas配体mRNA,含有穿孔素和颗粒酶B,并且在没有体外预刺激的情况下具有高细胞溶解活性。基于表型和功能特性,我们得出结论,记忆型 T 细胞和效应型 T 细胞可以作为人类 CD8+ T 细胞亚群中的不同实体分开。
Human CD8+ memory- and effector-type T cells are poorly defined. We show here that, next to a naive compartment, two discrete primed subpopulations can be found within the circulating human CD8+ T cell subset. First, CD45RA−CD45R0+ cells are reminiscent of memory-type T cells in that they express elevated levels of CD95 (Fas) and the integrin family members CD11a, CD18, CD29, CD49d, and CD49e, compared to naive CD8+ T cells, and are able to secrete not only interleukin (IL) 2 but also interferon γ, tumor necrosis factor α, and IL-4. This subset does not exert cytolytic activity without prior in vitro stimulation but does contain virus-specific cytotoxic T lymphocyte (CTL) precursors. A second primed population is characterized by CD45RA expression with concomitant absence of expression of the costimulatory molecules CD27 and CD28. The CD8+CD45RA+CD27− population contains T cells expressing high levels of CD11a, CD11b, CD18, and CD49d, whereas CD62L (L-selectin) is not expressed. These T cells do not secrete IL-2 or -4 but can produce IFN-γ and TNF-α. In accordance with this finding, cells contained within this subpopulation depend for proliferation on exogenous growth factors such as IL-2 and -15. Interestingly, CD8+CD45RA+CD27− cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation. Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.