1. Detection of HIV-1-specific gastrointestinal tissue resident CD8+ T-cells in chronic infection
- Author
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Kiniry, Brenna E, Li, Shengbin, Ganesh, Anupama, Hunt, Peter W, Somsouk, Ma, Skinner, Pamela J, Deeks, Steven G, and Shacklett, Barbara L
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Immunization ,Sexually Transmitted Infections ,Infectious Diseases ,HIV/AIDS ,Vaccine Related ,Vaccine Related (AIDS) ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,AIDS Vaccines ,Antigens ,CD ,Asymptomatic Diseases ,CD8-Positive T-Lymphocytes ,Chronic Disease ,Cytotoxicity ,Immunologic ,Gastrointestinal Tract ,HIV Infections ,HIV-1 ,Humans ,Immunologic Memory ,Immunophenotyping ,Integrin alpha Chains ,Lymphocyte Count ,Organ Specificity ,T-Box Domain Proteins ,Biological Sciences ,Medical and Health Sciences - 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-betLowEomesoderminNeg, 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. CD103Low CD8+ TRM primarily displayed a transitional memory phenotype and contained HIV-1-specific cells and cells expressing high levels of Eomesodermin, whereas CD103High CD8+ TRM primarily displayed an effector memory phenotype and were EomesoderminNeg. 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.
- Published
- 2018