Skeletal muscle antagonizes antiviral CD8⁺ T cell exhaustion.

ABSTRACT: CD8⁺ T cells become functionally impaired or "exhausted" in chronic infections, accompanied by unwanted body weight reduction and muscle mass loss. Whether muscle regulates T cell exhaustion remains incompletely understood. We report that mouse skeletal muscle increased interleukin (IL)-15 production during LCMV clone 13 chronic infection. Muscle-specific ablation of Il15 enhanced the CD8⁺ T cell exhaustion phenotype. Muscle-derived IL-15 was required to maintain a population of CD8⁺CD103⁺ muscle-infiltrating lymphocytes (MILs). MILs resided in a less inflamed microenvironment, expressed more T cell factor 1 (Tcf1), and had higher proliferative potential than splenic T cells. MILs differentiated into functional effector T cells after reent

SUBMITTER: Wu J 

PROVIDER: S-EPMC7292629 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature