CD8+ tissue-resident memory T-cell development depends on infection-matching regulatory T-cell types

Abstract

Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8⁺ memory T cells develop at the location of infection: tissue-resident memory T cells (T_RM). CD8⁺ T-cell responses are associated with type-1 infections and type-1 regulatory T cells (T_REG) are important for CD8⁺ T-cell development, however, if CD8⁺ T_RM cells develop under other infection types and require immune type-specific T_REG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8⁺ T_RM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching T_REG population contributing transforming growth factor-β. Nevertheless, type-1 T_REG cells remain the most important population for T_RM cell development. Once established, T_RM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8⁺ T_RM cells.