| First Author | Pack AD | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 3 | Pages | 573-578 |
| PubMed ID | 32591392 | Mgi Jnum | J:300405 |
| Mgi Id | MGI:6502358 | Doi | 10.4049/jimmunol.2000218 |
| Citation | Pack AD, et al. (2020) Cutting Edge: Augmenting Muscle MHC Expression Enhances Systemic Pathogen Control at the Expense of T Cell Exhaustion. J Immunol 205(3):573-578 |
| abstractText | Myocytes express low levels of MHC class I (MHC I), perhaps influencing the ability of CD8(+) T cells to efficiently detect and destroy pathogens that invade muscle. Trypanosoma cruzi infects many cell types but preferentially persists in muscle, and we asked if this tissue-dependent persistence was linked to MHC expression. Inducible enhancement of skeletal muscle MHC I in mice during the first 20 d of T. cruzi infection resulted in enhanced CD8-dependent reduction of parasite load. However, continued overexpression of MHC I beyond 30 d ultimately led to a collapse of systemic parasite control associated with immune exhaustion, which was reversible in part by blocking PD-1:PD-L1 interactions. These studies demonstrate a surprisingly strong and systemically dominant effect of skeletal muscle MHC expression on maintaining T cell function and pathogen control and argue that the normally low MHC I expression in skeletal muscle is host protective by allowing for pathogen control while preventing immune exhaustion. |
