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Tissue-resident memory (T RM ) 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 + T RM 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 + T RM 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 + T RM responses appeared strongest in individuals naturally controlling HIV-1 infection. Two CD8 + T RM subsets, distinguished by CD103 expression intensity, were identified. CD103 Low CD8 + T RM primarily displayed a transitional memory phenotype and contained HIV-1-specific cells and cells expressing high levels of Eomesodermin, whereas CD103 High CD8 + T RM 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 T RM contribute to the anti-HIV-1 immune response. Further exploration of CD8 + T RM will inform development of anti-HIV-1 immune-based therapies and vaccines targeted to the mucosa.

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