Mucosal immunology 2017 11 15() doi 10.1038/mi.2017.96
Tissue-resident memory (TRM) CD8(+) T-cells are non-recirculating, long-lived cells housed in tissues that can confer protection against mucosal pathogens. Human immunodeficiency virus-1 (HIV-1) is a mucosal pathogen and the gastrointestinal tract is an important site of viral pathogenesis and transmission. Thus, CD8(+) TRM cells may be an important effector subset for controlling HIV-1 in mucosal tissues. This study sought to determine the abundance, phenotype, and functionality of CD8(+) TRM cells in the context of chronic HIV-1 infection. We found that the majority of rectosigmoid CD8(+) T-cells were CD69(+)CD103(+)S1PR1(-) and T-bet(Low)Eomesodermin(Neg), indicative of a tissue-residency phenotype similar to that described in murine models. HIV-1-specific CD8(+) TRM responses appeared strongest in individuals naturally controlling HIV-1 infection. Two CD8(+) TRM subsets, distinguished by CD103 expression intensity, were identified. CD103(Low) CD8(+) TRM primarily displayed a transitional memory phenotype and contained HIV-1-specific cells and cells expressing high levels of Eomesodermin, whereas CD103(High) CD8(+) TRM primarily displayed an effector memory phenotype and were Eomesodermin(Neg). These findings suggest a large fraction of CD8(+) T-cells housed in the human rectosigmoid mucosa are tissue-resident and that TRM contribute to the anti-HIV-1 immune response. Further exploration of CD8(+) TRM will inform development of anti-HIV-1 immune-based therapies and vaccines targeted to the mucosa.Mucosal Immunology advance online publication 15 November 2017; doi:10.1038/mi.2017.96.