CD8αα intraepithelial lymphocytes arise from two main thymic precursors
| Autor: | Roland Ruscher, Kristin A. Hogquist, Stephen C. Jameson, Rebecca L Kummer, You Jeong Lee |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
education.field_of_study T cell Immunology Population T-cell receptor hemic and immune systems chemical and pharmacologic phenomena Biology Major histocompatibility complex CXCR3 Molecular biology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Antigen Intestinal mucosa biology.protein medicine Immunology and Allergy Intraepithelial lymphocyte education |
| Zdroj: | Nature Immunology. 18:771-779 |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/ni.3751 |
| Popis: | TCRαβ+CD4-CD8α+CD8β- intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ+CD4-CD8- thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1+ population and a T-bet+ population that accumulated with age. Both gave rise to intestinal CD8αα IELs after adoptive transfer. The PD-1+ IELp population included more strongly self-reactive clones and was largely restricted by classical major histocompatibility complex (MHC) molecules. Those cells localized to the cortex and efficiently emigrated in a manner dependent on the receptor S1PR1. The T-bet+ IELp population localized to the medulla, included cells restricted by non-classical MHC molecules and expressed the receptor NK1.1, the integrin CD103 and the chemokine receptor CXCR3. The two IELp populations further differed in their use of the T cell antigen receptor (TCR) α-chain variable region (Vα) and β-chain variable region (Vβ). These data provide a foundation for understanding the biology of CD8αα IELs. |
| Databáze: | OpenAIRE |
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