Journal of Hepatology 2020-Jan
Functions of human liver CD69+CD103-CD8+ T cells depend on HIF-2α activity in healthy and pathologic livers.
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कीवर्ड
सार
BACKGROUND & AIMS
Human liver CD69+CD8+ T cells are ∼95% CD103- and ∼5% CD103+. Although CD69+CD103+CD8+ T cells show tissue residency and robustly respond to antigens, CD69+CD103-CD8+ T cells are not yet well understood.RESULTS
Human liver CD69+CD103-CD8+ T cells exhibited a phenotype of tissue residency and terminal differentiation with HIF-2α upregulation. CD103- T cells included both hepatotropic and non-hepatotropic viruses-specific cells whereas CD103+ T cells did only hepatotropic virus-specific cells. Although CD103- cells were weaker effectors on a per cell basis than CD103+ cells following T-cell receptor or interleukin-15 stimulation, they remained the major CD69+CD8+ effector population in the liver, surviving with less cell death. HIF-2α inhibitor suppressed the effector functions and survival of CD69+CD103-CD8+ T cells. In addition, HIF-2α expression in liver CD69+CD103-CD8+ T cells was significantly increased in patients with AHA or LC.CONCLUSIONS
Liver CD69+CD103-CD8+ T cells have the phenotype of tissue residency and terminally differentiation, and their effector functions depends on HIF-2α. Furthermore, activation of liver CD69+CD103-CD8+ T cells with HIF-2α upregulation is observed during liver pathology.