TY - JOUR
T1 - Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties
AU - Billerbeck, Eva
AU - Kang, Yu Hoi
AU - Walker, Lucy
AU - Lockstone, Helen
AU - Grafmueller, Stefanie
AU - Fleming, Vicki
AU - Flint, Jonathan
AU - Willberg, Chris B.
AU - Bengsch, Bertram
AU - Seigel, Bianca
AU - Ramamurthy, Narayan
AU - Zitzmann, Nicole
AU - Barnes, Eleanor J.
AU - Thevanayagam, Jonarthan
AU - Bhagwanani, Anisha
AU - Leslie, Alasdair
AU - Oo, Ye H.
AU - Kollnberger, Simon
AU - Bowness, Paul
AU - Drognitz, Oliver
AU - Adams, David H.
AU - Blum, Hubert E.
AU - Thimme, Robert
AU - Klenerman, Paul
PY - 2010/2/16
Y1 - 2010/2/16
N2 - CD8+ T lymphocytes play a key role in host defense, in particular against important persistent viruses, although the critical functional properties of such cells in tissue are not fully defined.Wehave previously observed that CD8+ T cells specific for tissue-localized viruses such as hepatitis C virus express high levels of the C-type lectin CD161. To explore the significance of this, we examined CD8 +CD161+ T cells in healthy donors and those with hepatitis C virus and defined a population of CD8+ T cells with distinct homing and functional properties. These cells express high levels of CD161 and a pattern of molecules consistent with type 17 differentiation, including cytokines (e.g., IL-17, IL-22), transcription factors (e.g., retinoic acid-related orphan receptor γ-t, P = 6 × 10-9; RUNX2, P = 0.004), cytokine receptors (e.g., IL-23R, P = 2 × 10-7; IL-18 receptor, P = 4 × 10-6), and chemokine receptors (e.g., CCR6, P = 3 × 10-8; CXCR6, P = 3 × 10-7; CCR2, P = 4 × 10-7). CD161+CD8+ T cells were markedly enriched in tissue samples and coexpressed IL-17 with high levels of IFN-γ and/or IL-22. The levels of polyfunctional cells in tissue was most marked in those with mild disease (P = 0.0006). These data define a T cell lineage that is present already in cord blood and represents as many as one in six circulating CD8+ T cells in normal humans and a substantial fraction of tissue-infiltrating CD8+ T cells in chronic in.ammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man.
AB - CD8+ T lymphocytes play a key role in host defense, in particular against important persistent viruses, although the critical functional properties of such cells in tissue are not fully defined.Wehave previously observed that CD8+ T cells specific for tissue-localized viruses such as hepatitis C virus express high levels of the C-type lectin CD161. To explore the significance of this, we examined CD8 +CD161+ T cells in healthy donors and those with hepatitis C virus and defined a population of CD8+ T cells with distinct homing and functional properties. These cells express high levels of CD161 and a pattern of molecules consistent with type 17 differentiation, including cytokines (e.g., IL-17, IL-22), transcription factors (e.g., retinoic acid-related orphan receptor γ-t, P = 6 × 10-9; RUNX2, P = 0.004), cytokine receptors (e.g., IL-23R, P = 2 × 10-7; IL-18 receptor, P = 4 × 10-6), and chemokine receptors (e.g., CCR6, P = 3 × 10-8; CXCR6, P = 3 × 10-7; CCR2, P = 4 × 10-7). CD161+CD8+ T cells were markedly enriched in tissue samples and coexpressed IL-17 with high levels of IFN-γ and/or IL-22. The levels of polyfunctional cells in tissue was most marked in those with mild disease (P = 0.0006). These data define a T cell lineage that is present already in cord blood and represents as many as one in six circulating CD8+ T cells in normal humans and a substantial fraction of tissue-infiltrating CD8+ T cells in chronic in.ammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man.
KW - Arthritis
KW - Hepatitis
KW - Hepatitis C virus
KW - IL-17
KW - IL-22
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U2 - 10.1073/pnas.0914839107
DO - 10.1073/pnas.0914839107
M3 - Article
C2 - 20133607
AN - SCOPUS:77649253219
SN - 0027-8424
VL - 107
SP - 3006
EP - 3011
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -