CD8αα memory effector T cells descend directly from clonally expanded CD8α+βhigh TCRαβ T cells in vivo
CD8αα memory effector T cells descend directly from clonally expanded CD8α+βhigh TCRαβ T cells in vivo
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DOI：
10.1182/blood-2002-04-1136
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发表时间：
2002-12-01
期刊：
影响因子：
20.3
通讯作者：
Koizumi, S
中科院分区：
文献类型：
--
作者：
Konno, A;Okada, K;Koizumi, S
尽管在健康个体中大多数外周CD 8（+）α T细胞高度表达CD 8 α异二聚体，但在HIV感染或Wiskott-Aldrich综合征和骨髓移植后，CD 8 α（+）β（低）或CD 8 α T细胞增加。这些不常见的细胞群的意义还没有得到很好的理解。关于这些亚群和CD 8 α（+）β（高）细胞是否属于不同的个体发生谱系，或者是否一部分CD 8 α（+）β（高）细胞具有下调的CD 8 β链，存在一些问题。在这里，我们评估了CD 8 α α和CD 8 α（+）β（低）α T细胞的克隆性以及它们的表型和功能特征。从表面抗原、细胞毒性颗粒成分和细胞因子产生推断，CD 8 α（+）β（低）细胞仅由效应记忆细胞组成。CD 8 α α细胞包括效应记忆细胞和终末分化的CD 45 RO（-）CCR 7（-）记忆细胞。T细胞受体（TCR）V β互补决定区3（CDR 3）光谱分析和随后的CDR 3 cDNA克隆测序显示了CD 8 α（+）β（高）细胞的多克隆性以及CD 8 α（+）β（低）和CD 8 α α细胞的寡克隆性。重要的是，在CD 8 α（+）β（高）和CD 8 α（+）β（高）亚群中也鉴定了CD 8 α细胞内的一些扩增克隆。此外，信号联合TCR重排切除环浓度随着CD 8 β表达的丧失而降低。这些结果表明，一些特定的CD 8 α（+）β（高）α-T细胞克隆性扩增，分化，并同时下调CD 8 β链可能通过抗原驱动的机制。如果抗原刺激直接影响CD 8 α T细胞的出现，这些细胞，以前一直被认为是胸腺外起源，可能会提出新的见解，自身免疫性疾病和免疫缺陷的机制，也作为一个有用的生物标志物，以评估疾病的活动。(C)2002年，美国血液学会。
Whereas most peripheral CD8(+) alphabeta T cells highly express CD8alphabeta heterodimer in healthy individuals, there is an increase of CD8alpha(+)beta(low) or CD8alphaalpha alphabeta T cells in HIV infection or Wiskott-Aldrich syndrome and after bone marrow transplantation. The significance of these uncommon cell populations is not well understood. There has been some question as to whether these subsets and CD8alpha(+)beta(high) cells belong to different ontogenic lineages or whether a fraction of CD8alpha(+)beta(high) cells have down-regulated CD8beta chain. Here we assessed clonality of CD8alphaalpha and CD8alpha(+)beta(low) alphabeta T cells as well as their phenotypic and functional characteristics. Deduced from surface antigens, cytotoxic granule constituents, and cytokine production, CD8alpha(+)beta(low) cells are exclusively composed of effector memory cells. CD8alphaalpha cells comprise effector memory cells and terminally differentiated CD45RO(-)CCR7(-) memory cells. T-cell receptor (TCR) Vbeta complementarity-determining region 3 (CDR3) spectratyping analysis and subsequent sequencing of CDR3 cDNA clones revealed polyclonality of CD8alpha(+)beta(high) cells and oligoclonality of CD8alpha(+)beta(low) and CD8alphaalpha cells. Importantly, some expanded clones within CD8alphaalpha cells were also identified within CD8alpha(+)beta(high) and CD8alpha(+)beta(high) subpopulations. Furthermore, signal-joint TCR rearrangement excision circles concentration was reduced with the loss of CD8beta expression. These results indicated that some specific CD8alpha(+)beta(high) alphabeta T cells expand clonally, differentiate, and simultaneously down-regulate CD8beta chain possibly by an antigen-driven mechanism. Provided that antigenic stimulation directly influences the emergence of CD8alphaalpha alphabeta T cells, these cells, which have been previously regarded as of extrathymic origin, may present new insights into the mechanisms of autoimmune diseases and immunodeficiencies, and also serve as a useful biomarker to evaluate the disease activities. (C) 2002 by The American Society of Hematology.