CD8alpha alpha memory effector T cells descend directly from clonally expanded CD8alpha +beta high TCRalpha beta T cells in vivo.
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(low) 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.
Konno
Akihiro
A
Department of Pediatrics, Angiogenesis and Vascular Development, Graduate School of Medical Science and School of Medicine, Kanazawa University, Japan.
Okada
Kanae
K
Mizuno
Kazunori
K
Nishida
Mika
M
Nagaoki
Shuya
S
Toma
Tomoko
T
Uehara
Takahiro
T
Ohta
Kazuhide
K
Kasahara
Yoshihito
Y
Seki
Hidetoshi
H
Yachie
Akihiro
A
Koizumi
Shoichi
S
D000328:Adult; D000367:Age Factors; D016827:CD8 Antigens / Q000032:analysis*; D002455:Cell Division / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002675:Child, Preschool; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D008562:Membrane Glycoproteins / Q000032:analysis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology* / Q000276:immunology
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin