Analysis of CD161 expression on human CD8+T cells defines a distinct functional subset with tissue-homing properties
Open Access
- 28 January 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 107 (7), 3006-3011
- https://doi.org/10.1073/pnas.0914839107
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.Keywords
This publication has 50 references indexed in Scilit:
- Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammationThe Journal of Experimental Medicine, 2009
- PILAR is a novel modulator of human T-cell expansionBlood, 2008
- Human interleukin 17–producing cells originate from a CD161+CD4+ T cell precursorThe Journal of Experimental Medicine, 2008
- Anomalous Type 17 Response to Viral Infection by CD8 + T Cells Lacking T-bet and EomesoderminScience, 2008
- IL-22 mediates mucosal host defense against Gram-negative bacterial pneumoniaNature Medicine, 2008
- T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγImmunity, 2008
- Interleukin-22 but Not Interleukin-17 Provides Protection to Hepatocytes during Acute Liver InflammationImmunity, 2007
- CC Chemokine Receptor 5 and CXC Chemokine Receptor 6 Expression by Lung CD8+ Cells Correlates with Chronic Obstructive Pulmonary Disease SeverityThe American Journal of Pathology, 2007
- Analysis of Hepatitis C Virus Superinfection Exclusion by Using Novel Fluorochrome Gene-Tagged Viral GenomesJournal of Virology, 2007
- Intravascular Immune Surveillance by CXCR6+ NKT Cells Patrolling Liver SinusoidsPLoS Biology, 2005