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| Content Provider | PubMed Central |
|---|---|
| Author | Billerbeck, Eva Kang, Yu-hoi Walker, Lucy Helen, Lockstone Stefanie, Grafmueller Fleming, Vicki Flint, Jonathan Willberg, Chris B. Bengsch, Bertram Seigel, Bianca Ramamurthy, Narayan Zitzmann, Nicole Barnes, Eleanor J. Thevanayagam, Jonarthan Bhagwanani, Anisha Leslie, Alasdair Oo, Ye H. Simon, Kollnberger Bowness, Paul Oliver, Drognitz Adams, David H. Blum, Hubert E. Thimme, Robert Klenerman, Paul |
| Abstract | 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 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 inflammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man. |
| Related Links | http://dx.doi.org/10.1073/pnas.0914839107 |
| Ending Page | 3011 |
| Page Count | 6 |
| Starting Page | 3006 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 107 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2010-02-16 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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