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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. We have 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 gamma-t, P = 6 x 10(-9); RUNX2, P = 0.004), cytokine receptors (e.g., IL-23R, P = 2 x 10(-7); IL-18 receptor, P = 4 x 10(-6)), and chemokine receptors (e.g., CCR6, P = 3 x 10(-8); CXCR6, P = 3 x 10(-7); CCR2, P = 4 x 10(-7)). CD161(+)CD8(+) T cells were markedly enriched in tissue samples and coexpressed IL-17 with high levels of IFN-gamma 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 inflammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man.

Original publication

DOI

10.1073/pnas.0914839107

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

02/2010

Volume

107

Pages

3006 - 3011

Addresses

Department of Medicine II and Spemann Graduate School of Biology and Medicine, University of Freiburg, 79106 Freiburg, Germany.

Keywords

T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Cell Line, Fetal Blood, Humans, Hepacivirus, Hepatitis C, Luciferases, Alanine Transaminase, Receptors, Cytokine, Cytokines, Fluorescent Antibody Technique, Flow Cytometry, Reverse Transcriptase Polymerase Chain Reaction, Immunophenotyping, NK Cell Lectin-Like Receptor Subfamily B