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

Brenna E. Kiniry, Shengbin Li, Anupama Ganesh, Peter W. Hunt, Ma Somsouk, Pamela J. Skinner, Steven G. Deeks, Barbara L. Shacklett

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)909-920
Number of pages12
JournalMucosal Immunology
Volume11
Issue number3
DOIs
StatePublished - May 1 2018

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HIV-1
T-Lymphocytes
Infection
Phenotype
Mucous Membrane
Virus Diseases
Active Immunotherapy
Internship and Residency
Gastrointestinal Tract

Cite this

Kiniry, B. E., Li, S., Ganesh, A., Hunt, P. W., Somsouk, M., Skinner, P. J., ... Shacklett, B. L. (2018). Detection of HIV-1-specific gastrointestinal tissue resident CD8 + T-cells in chronic infection. Mucosal Immunology, 11(3), 909-920. https://doi.org/10.1038/mi.2017.96

Detection of HIV-1-specific gastrointestinal tissue resident CD8 + T-cells in chronic infection. / Kiniry, Brenna E.; Li, Shengbin; Ganesh, Anupama; Hunt, Peter W.; Somsouk, Ma; Skinner, Pamela J.; Deeks, Steven G.; Shacklett, Barbara L.

In: Mucosal Immunology, Vol. 11, No. 3, 01.05.2018, p. 909-920.

Research output: Contribution to journalArticle

Kiniry, BE, Li, S, Ganesh, A, Hunt, PW, Somsouk, M, Skinner, PJ, Deeks, SG & Shacklett, BL 2018, 'Detection of HIV-1-specific gastrointestinal tissue resident CD8 + T-cells in chronic infection', Mucosal Immunology, vol. 11, no. 3, pp. 909-920. https://doi.org/10.1038/mi.2017.96
Kiniry, Brenna E. ; Li, Shengbin ; Ganesh, Anupama ; Hunt, Peter W. ; Somsouk, Ma ; Skinner, Pamela J. ; Deeks, Steven G. ; Shacklett, Barbara L. / Detection of HIV-1-specific gastrointestinal tissue resident CD8 + T-cells in chronic infection. In: Mucosal Immunology. 2018 ; Vol. 11, No. 3. pp. 909-920.
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