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 (TRM). CD8+ T-cell responses are associated with type-1 infections and type-1 regulatory T cells (TREG) are important for CD8+ T-cell development, however, if CD8+ TRM cells develop under other infection types and require immune type-specific TREG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8+ TRM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching TREG population contributing transforming growth factor-β. Nevertheless, type-1 TREG cells remain the most important population for TRM cell development. Once established, TRM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8+ TRM cells.

Tissue-resident memory T cells: decoding intra-organ diversity with a gut perspective

“…Mechanistically, Treg that express functional TGF-β-activating integrin αvβ8 [ 25 ] are recruited to the site of inflammation via cysteine-X-cysteine chemokine receptor 3 (CXCR3), and localized in close proximity to CD8 + T cells, making bioactive TGF-β locally available and promoting CD8 + T RM development [ 26 ]. The establishment of T RM depends on the presence of Treg that match the type of local infection, among which type 1 Treg are the most important population for T RM development [ 27 ]. Notably, sustained TGF-β requirement for CD8 + T RM formation depends on the tissue: it is crucial for the skin, gut and salivary gland, but not for kidney, adipose tissue, and liver [ 19 , 28 ].…”

FOXP3+ Regulatory T Cells Require TBET to Regulate Activated CD8+ T Cells During Recovery from Influenza Infection

“…Following influenza infection, CD4+ T cells are required for the formation of lung-resident Trm cells (3). Emerging evidence has implicated CD4+ FOXP3+ regulatory T (Treg) cells in Trm development in the lungs and other tissues (4,5). Following viral clearance, Treg cells resolve inflammation to promote recovery from influenza ( 6), but their effect on the Trm compartment during recovery from influenza is unknown.…”