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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-04-1136.
Submitted April 15, 2002
Accepted July 8, 2002
CD8 memory effector T cells descend directly from clonally expanded CD8+ßhigh TCRß 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
Department of Pediatrics, Angiogenesis and Vascular Development, Kanazawa University, Graduate School of Medical Science and School of Medicine, Kanazawa, Japan; Department of Pediatrics, Angiogenesis and Vascular Development, Kanazawa University, Graduate School of Medical Science and School of Medicine, Kanazawa, Japan
Department of Laboratory Sciences, Kanazawa University, Faculty of Medicine, School of Health Sciences, Kanazawa, Japan
Department of Pediatrics, Angiogenesis and Vascular Development, Kanazawa University, Graduate School of Medical Science and School of Medicine, Kanazawa, Japan
Department of Laboratory Sciences, Kanazawa University, Faculty of Medicine, School of Health Sciences, Kanazawa, Japan; Department of Pediatrics, Angiogenesis and Vascular Development, Kanazawa University, Graduate School of Medical Science and School of Medicine, Kanazawa, Japan
* Corresponding author; email: yachie{at}med.kanazawa-u.ac.jp.
While most peripheral CD8+ ßT cells highly express CD8ß heterodimer in healthy individuals, there is an increase of CD8+ßlow or CD8 ßT cells in human immunodeficiency virus infection, 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+ßhigh cells belong to different ontogenic lineages, or a fraction of CD8+ßhigh cells have downregulated CD8ß chain. Here we assessed clonality of CD8 and CD8+ßlow ßT cells as well as their phenotypic and functional characteristics. Deduced from surface antigens, cytotoxic granule constituents, and cytokine production, CD8+ßlow cells are exclusively composed of effector memory cells. CD8 cells comprise effector memory cells and terminally differentiated CD45RO-CCR7- memory cells. TCR Vß complementarity-determining region 3 (CDR3) spectratyping analysis and subsequent sequencing of CDR3 cDNA clones revealed polyclonality of CD8+ßhigh cells and oligoclonality of CD8+ßlow and CD8 cells. Importantly, some expanded clones within CD8 cells were also identified within CD8+ßhigh and CD8+ßlow subpopulations. Furthermore, signal-joint T cell receptor rearrangement excision circles concentration was reduced with the loss of CD8ß expression. These results indicated that some specific CD8+ßhigh ßT cells expand clonally, differentiate, and simultaneously downregulate CD8ß chain possibly by antigen-driven mechanism. Provided that antigenic stimulation directly influence the emergence of CD8 ßT 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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