UCSF

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^LowEomesodermin^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.