Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion
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)-...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
12 June 2020
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| In: |
Science advances
Year: 2020, Volume: 6, Issue: 24 |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aba3458 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/sciadv.aba3458 Verlag, lizenzpflichtig, Volltext: https://advances.sciencemag.org/content/6/24/eaba3458 
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| Author Notes: | Jingxia Wu, Nina Weisshaar, Agnes Hotz-Wagenblatt, Alaa Madi, Sicong Ma, Alessa Mieg, Marvin Hering, Kerstin Mohr, Tilo Schlimbach, Helena Borgers, Guoliang Cui |
| Summary: | 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. |
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| Item Description: | Im Titel ist das Zeichen + hochgestellt Gesehen am 13.08.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aba3458 |