CD8 ⁺ T cells induce cachexia during chronic viral infection

Abstract

Cachexia represents a leading cause of morbidity and mortality in various cancers, chronic inflammation and infections. Understanding of the mechanisms that drive cachexia has remained limited, especially for infection-associated cachexia (IAC). Here we describe a model of reversible cachexia in mice with chronic viral infection and identify an essential role for CD8 ⁺ T cells in IAC. Cytokines linked to cancer-associated cachexia did not contribute to IAC. Instead, virus-specific CD8 ⁺ T cells caused morphological and molecular changes in the adipose tissue, which led to depletion of lipid stores. These changes occurred at a time point that preceded the peak of the CD8 ⁺ T cell response and required T cell–intrinsic type 1 interferon signaling and antigen-specific priming. Our results link systemic antiviral immune responses to adipose-tissue remodeling and reveal an underappreciated role of CD8 ⁺ T cells in IAC.