Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion

• Verfasst von: Wu, Jingxia [VerfasserIn]
• Verfasst von: Hotz-Wagenblatt, Agnes [VerfasserIn]
• Verfasst von: Hering, Marvin [VerfasserIn]
• Verfasst von: Cui, Guoliang [VerfasserIn]
• Titel: Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion
• Verf.angabe: Jingxia Wu, Nina Weisshaar, Agnes Hotz-Wagenblatt, Alaa Madi, Sicong Ma, Alessa Mieg, Marvin Hering, Kerstin Mohr, Tilo Schlimbach, Helena Borgers, Guoliang Cui
• E-Jahr: 2020
• Jahr: 12 June 2020
• Umfang: 11 S.
• Fussnoten: Im Titel ist das Zeichen + hochgestellt ; Gesehen am 13.08.2020
• Titel Quelle: Enthalten in: Science advances
• Ort Quelle: Washington, DC [u.a.] : Assoc., 2015
• Jahr Quelle: 2020
• Band/Heft Quelle: 6(2020,24) Artikel-Nummer eaba3458, 12 Seiten
• ISSN Quelle: 2375-2548
• DOI: doi:10.1126/sciadv.aba3458
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cachexia
• Sach-SW: disease
• Sach-SW: lymphocytic choriomeningitis virus
• Sach-SW: mice
• Sach-SW: persistence
• Sach-SW: proliferation
• Sach-SW: rna
• K10plus-PPN: 1727031385

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 //15 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 reentering lymphoid tissues. Increasing muscle mass via muscle-specific inhibition of TGF beta signaling enhanced IL-15 production and antiviral CD8(+) T cell responses. We conclude that skeletal muscle antagonizes T cell exhaustion by protecting T cell proliferative potential from inflammation and replenishing the effector T cell progeny pool in lymphoid organs.