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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-04-1136.
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Blood, 1 December 2002, Vol. 100, No. 12, pp. 4090-4097
IMMUNOBIOLOGY
CD8 memory effector T cells descend directly from clonally
expanded CD8+ high TCR T cells
in vivo
Akihiro Konno,
Kanae Okada,
Kazunori Mizuno,
Mika Nishida,
Shuya Nagaoki,
Tomoko Toma,
Takahiro Uehara,
Kazuhide Ohta,
Yoshihito Kasahara,
Hidetoshi Seki,
Akihiro Yachie, and
Shoichi Koizumi
From the Department of Pediatrics, Angiogenesis and
Vascular Development, Graduate School of Medical Science and School of
Medicine, Kanazawa University and School of Health Sciences, Faculty of
Medicine, Kanazawa University, Kanazawa, Japan.
Whereas most peripheral CD8+   T cells highly
express CD8 heterodimer in healthy individuals, there is an
increase of CD8+low or CD8 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 CD8+high cells
belong to different ontogenic lineages or whether a fraction of
CD8+high cells have down-regulated CD8
chain. Here we assessed clonality of CD8 and
CD8+low T cells as well as their
phenotypic and functional characteristics. Deduced from surface
antigens, cytotoxic granule constituents, and cytokine production,
CD8+low cells are exclusively composed of
effector memory cells. CD8 cells comprise effector memory cells
and terminally differentiated CD45RO CCR7
memory cells. T-cell receptor (TCR) V complementarity-determining region 3 (CDR3) spectratyping analysis and subsequent sequencing of
CDR3 cDNA clones revealed polyclonality of
CD8+high cells and oligoclonality of
CD8+low and CD8 cells. Importantly,
some expanded clones within CD8 cells were also identified within
CD8+high and
CD8+low subpopulations. Furthermore,
signal-joint TCR rearrangement excision circles concentration was
reduced with the loss of CD8 expression. These results indicated
that some specific CD8+high T
cells expand clonally, differentiate, and simultaneously down-regulate
CD8 chain possibly by an antigen-driven mechanism. Provided that
antigenic stimulation directly influences the emergence of CD8
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.
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