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.
Bibliographical noteFunding Information:
We thank Rebecca Hoh, Montha Pao, Monika Deswal, and the clinical staff at San Francisco General Hospital for their assistance with participant recruitment and sample collection. We thank the participants for their willingness to contribute to this study. The SCOPE cohort was supported by the Delaney AIDS Research Enterprise (DARE; AI096109 and AI127966), NIAID (K24 AI069994), and the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763). We also thank Dr Alex Khoruts, University of Minnesota, for assistance with identification of anatomical compartments in rectosigmoid tissue samples. This work was supported by NIH/NIAID R01-AI057020 to B.L.S. The UC Davis Flow Cytometry Shared Resource Laboratory (FCSR) was supported by grants from the National Institutes of Health: NCI P30 CA0933730, and NIH NCRR C06-RR12088, S10-RR12964, S10-RR026825, and S10-OD018223-01A1; and the James B. Pendleton Charitable Trust. We thank the FCSR staff members Ms. Bridget McLaughlin and Mr Jonathan Van Dyke, for assistance with flow cytometry.