CD8αα memory effector T cells descend directly from clonally expanded CD8α+βhigh TCRαβ T cells in vivo

被引:52
作者
Konno, A
Okada, K
Mizuno, K
Nishida, M
Nagaoki, S
Toma, T
Uehara, T
Ohta, K
Kasahara, Y
Seki, H
Yachie, A
Koizumi, S
机构
[1] Kanazawa Univ, Grad Sch Med Sci, Dept Pediat Angiogenesis & Vasc Dept, Kanazawa, Ishikawa 920, Japan
[2] Kanazawa Univ, Sch Med, Kanazawa, Ishikawa 920, Japan
[3] Kanazawa Univ, Sch Hlth Sci, Fac Med, Kanazawa, Ishikawa 920, Japan
关键词
D O I
10.1182/blood-2002-04-1136
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:4090 / 4097
页数:8
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