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Publication : CD8αα intraepithelial lymphocytes arise from two main thymic precursors.

First Author  Ruscher R Year  2017
Journal  Nat Immunol Volume  18
Issue  7 Pages  771-779
PubMed ID  28530714 Mgi Jnum  J:259590
Mgi Id  MGI:6141980 Doi  10.1038/ni.3751
Citation  Ruscher R, et al. (2017) CD8alphaalpha intraepithelial lymphocytes arise from two main thymic precursors. Nat Immunol 18(7):771-779
abstractText  TCRalphabeta(+)CD4(-)CD8alpha(+)CD8beta(-) intestinal intraepithelial lymphocytes (CD8alphaalpha 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 TCRbeta(+)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 CD8alphaalpha 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) alpha-chain variable region (Valpha) and beta-chain variable region (Vbeta). These data provide a foundation for understanding the biology of CD8alphaalpha IELs.
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