Detection of HIV-1-Specific Gastrointestinal Tissue Resident CD8(+) T-cells in Chronic Infection

Tissue-resident memory (T(RM)) CD8(+) T-cells are non-recirculating, long-lived cells housed in tissues that can confer protection against mucosal pathogens. 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.