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 language | English (US) |
|---|---|
| Pages (from-to) | 909-920 |
| Number of pages | 12 |
| Journal | Mucosal Immunology |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Detection of HIV-1-specific gastrointestinal tissue resident CD8 + T-cells in chronic infection
AU - Kiniry, Brenna E.
AU - Li, Shengbin
AU - Ganesh, Anupama
AU - Hunt, Peter W.
AU - Somsouk, Ma
AU - Skinner, Pamela J.
AU - Deeks, Steven G.
AU - Shacklett, Barbara L.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
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U2 - 10.1038/mi.2017.96
DO - 10.1038/mi.2017.96
M3 - Article
C2 - 29139476
AN - SCOPUS:85044755564
VL - 11
SP - 909
EP - 920
JO - Mucosal Immunology
JF - Mucosal Immunology
SN - 1933-0219
IS - 3
ER -