Skewed maturation of memory HIV-specific CD8 T lymphocytes
Skewed maturation of memory HIV-specific CD8 T lymphocytes
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DOI：
10.1038/35065118
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发表时间：
2001-03-01
期刊：
影响因子：
64.8
通讯作者：
Pantaleo, G
中科院分区：
文献类型：
--
作者：
Champagne, P;Ogg, GS;Pantaleo, G
理解记忆性T细胞的谱系分化是免疫学的一个核心问题。我们通过分析趋化因子受体CCR7的表达来研究这一问题，CCR7定义了具有不同归巢和效应能力的初始T淋巴细胞和记忆T淋巴细胞的不同亚群（1 - 3）以及针对人类免疫缺陷病毒（HIV）和巨细胞病毒的抗病毒免疫反应。对CD45RA和CCR7抗原表达的体外分析，以及对不同记忆性CD8(+) T细胞群的细胞分裂能力的体外分析，确定了HIV特异性和巨细胞病毒特异性CD8(+) T淋巴细胞的四个亚群，并表明了以下谱系分化模式：CD45RA(+)CCR7(+)→CD45RA(-)CCR7(+)→CD45RA(-)CCR7(-)→CD45RA(+)CCR7(-)。在此，我们通过对细胞分裂的分析（主要局限于CCR7(+) CD8(+) T细胞亚群）证明，抗原特异性CD8(+) T细胞的分化是一个两步过程，其特征首先是一个增殖阶段，主要局限于CCR7(+) CD8(+)细胞亚群，随后是一个功能成熟阶段，包括CCR7(-) CD8(+)细胞亚群。这些群体在HIV特异性和巨细胞病毒特异性CD8(+) T细胞中的分布表明，HIV特异性细胞群主要（70%）由终末分化前的CD45RA(-)CCR7(-)细胞组成，而巨细胞病毒特异性细胞群主要（50%）由终末分化的CD45RA(+)CCR7(-)细胞组成。这些结果表明在HIV感染期间HIV特异性记忆性CD8(+) T细胞的成熟出现偏移。
Understanding the lineage differentiation of memory T cells is a central question in immunology. We investigated this issue by analysing the expression of the chemokine receptor CCR7, which defines distinct subsets of naive and memory T lymphocytes with different homing and effector capacities(1-3) and antiviral immune responses to HIV and cytomegalovirus. Ex vivo analysis of the expression of CD45RA and CCR7 antigens, together with in vitro analysis of the cell-division capacity of different memory CD8(+) T-cell populations, identified four subsets of HIV- and CMV-specific CD8(+) T lymphocytes, and indicated the following lineage differentiation pattern: CD45RA(+)CCR7(+) --> CD45RA(-) CCR7(+) --> CD45RA(-) CCR7(-) --> CD45RA(+) CCR7(-). Here we demonstrate through analysis of cell division (predominantly restricted to the CCR7(+) CD8(+) T-cell subsets) that the differentiation of antigen-specific CD8(+) T cells is a two-step process characterized initially by a phase of proliferation largely restricted to the CCR7(+) CD8(+) cell subsets, followed by a phase of functional maturation encompassing the CCR7(-) CD8(+) cell subsets. The distribution of these populations in HIV- and CMV-specific CD8(+) T cells showed that the HIV-specific cell pool was predominantly (70%) composed of pre-terminally differentiated CD45RA(-)CCR7(-) cells, whereas the CMV-specific cell pool consisted mainly (50%) of the terminally differentiated CD45RA(+) CCR7(-) cells. These results demonstrate a skewed maturation of HIV-specific memory CD8(+) T cells during HIV infection.