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Detection of HIV-1-specific gastrointestinal tissue resident CD8(+) T-cells in chronic infection.

Detection of HIV-1-specific gastrointestinal tissue resident CD8(+) T-cells in chronic infection.
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Kiniry BE, Li S, Ganesh A, Hunt PW, Somsouk M, Skinner PJ, Deeks SG, Shacklett BL,


Kiniry BE, Li S, Ganesh A, Hunt PW, Somsouk M, Skinner PJ, Deeks SG, Shacklett BL, (click to view)

Kiniry BE, Li S, Ganesh A, Hunt PW, Somsouk M, Skinner PJ, Deeks SG, Shacklett BL,

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Mucosal immunology 2017 11 15() doi 10.1038/mi.2017.96

Abstract

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.

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