MAIT cells upregulate α4β7 in response to acute simian immunodeficiency Virus/Simian HIV infection but are resistant to peripheral depletion in pigtail macaques

Jennifer A. Juno, Kathleen M. Wragg, Thakshila Amarasena, Bronwyn S. Meehan, Jeffrey Y.W. Mak, Ligong Liu, David P. Fairlie, James McCluskey, Sidonia B.G. Eckle, Stephen J. Kent

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Abstract

Mucosal-associated invariant T (MAIT) cells are nonconventional T lymphocytes that recognize bacterial metabolites presented by MR1. Whereas gut bacterial translocation and the loss/dysfunction of peripheral MAIT cells in HIV infection is well described, MAIT cells in nonhuman primate models are poorly characterized.We generated a pigtail macaque (PTM)-specific MR1 tetramer and characterized MAIT cells in serial samples from naive and SIV- or simian HIV-infected PTM. Although PTM MAIT cells generally resemble the phenotype and transcriptional profile of human MAIT cells, they exhibited uniquely low expression of the gut-homing marker α4β7 and were not enriched at the gut mucosa. PTM MAIT cells responded to SIV/simian HIV infection by proliferating and upregulating α4β7, coinciding with increased MAIT cell frequency in the rectum. By 36 wk of infection, PTM MAIT cells were activated and exhibited a loss of Tbet expression but were not depleted as in HIV infection. Our data suggest the following: 1) MAIT cell activation and exhaustion is uncoupled from the hallmark depletion of MAIT cells during HIV infection; and 2) the lack of PTM MAIT cell enrichment at the gut mucosa may prevent depletion during chronic infection, providing a model to assess potential immunotherapeutic approaches to modify MAIT cell trafficking during HIV infection.

Original languageEnglish
Pages (from-to)2105-2120
Number of pages16
JournalJournal of Immunology
Volume202
Issue number7
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

Juno, Jennifer A. ; Wragg, Kathleen M. ; Amarasena, Thakshila ; Meehan, Bronwyn S. ; Mak, Jeffrey Y.W. ; Liu, Ligong ; Fairlie, David P. ; McCluskey, James ; Eckle, Sidonia B.G. ; Kent, Stephen J. / MAIT cells upregulate α4β7 in response to acute simian immunodeficiency Virus/Simian HIV infection but are resistant to peripheral depletion in pigtail macaques. In: Journal of Immunology. 2019 ; Vol. 202, No. 7. pp. 2105-2120.
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abstract = "Mucosal-associated invariant T (MAIT) cells are nonconventional T lymphocytes that recognize bacterial metabolites presented by MR1. Whereas gut bacterial translocation and the loss/dysfunction of peripheral MAIT cells in HIV infection is well described, MAIT cells in nonhuman primate models are poorly characterized.We generated a pigtail macaque (PTM)-specific MR1 tetramer and characterized MAIT cells in serial samples from naive and SIV- or simian HIV-infected PTM. Although PTM MAIT cells generally resemble the phenotype and transcriptional profile of human MAIT cells, they exhibited uniquely low expression of the gut-homing marker α4β7 and were not enriched at the gut mucosa. PTM MAIT cells responded to SIV/simian HIV infection by proliferating and upregulating α4β7, coinciding with increased MAIT cell frequency in the rectum. By 36 wk of infection, PTM MAIT cells were activated and exhibited a loss of Tbet expression but were not depleted as in HIV infection. Our data suggest the following: 1) MAIT cell activation and exhaustion is uncoupled from the hallmark depletion of MAIT cells during HIV infection; and 2) the lack of PTM MAIT cell enrichment at the gut mucosa may prevent depletion during chronic infection, providing a model to assess potential immunotherapeutic approaches to modify MAIT cell trafficking during HIV infection.",
author = "Juno, {Jennifer A.} and Wragg, {Kathleen M.} and Thakshila Amarasena and Meehan, {Bronwyn S.} and Mak, {Jeffrey Y.W.} and Ligong Liu and Fairlie, {David P.} and James McCluskey and Eckle, {Sidonia B.G.} and Kent, {Stephen J.}",
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MAIT cells upregulate α4β7 in response to acute simian immunodeficiency Virus/Simian HIV infection but are resistant to peripheral depletion in pigtail macaques. / Juno, Jennifer A.; Wragg, Kathleen M.; Amarasena, Thakshila; Meehan, Bronwyn S.; Mak, Jeffrey Y.W.; Liu, Ligong; Fairlie, David P.; McCluskey, James; Eckle, Sidonia B.G.; Kent, Stephen J.

In: Journal of Immunology, Vol. 202, No. 7, 01.01.2019, p. 2105-2120.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - MAIT cells upregulate α4β7 in response to acute simian immunodeficiency Virus/Simian HIV infection but are resistant to peripheral depletion in pigtail macaques

AU - Juno, Jennifer A.

AU - Wragg, Kathleen M.

AU - Amarasena, Thakshila

AU - Meehan, Bronwyn S.

AU - Mak, Jeffrey Y.W.

AU - Liu, Ligong

AU - Fairlie, David P.

AU - McCluskey, James

AU - Eckle, Sidonia B.G.

AU - Kent, Stephen J.

PY - 2019/1/1

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N2 - Mucosal-associated invariant T (MAIT) cells are nonconventional T lymphocytes that recognize bacterial metabolites presented by MR1. Whereas gut bacterial translocation and the loss/dysfunction of peripheral MAIT cells in HIV infection is well described, MAIT cells in nonhuman primate models are poorly characterized.We generated a pigtail macaque (PTM)-specific MR1 tetramer and characterized MAIT cells in serial samples from naive and SIV- or simian HIV-infected PTM. Although PTM MAIT cells generally resemble the phenotype and transcriptional profile of human MAIT cells, they exhibited uniquely low expression of the gut-homing marker α4β7 and were not enriched at the gut mucosa. PTM MAIT cells responded to SIV/simian HIV infection by proliferating and upregulating α4β7, coinciding with increased MAIT cell frequency in the rectum. By 36 wk of infection, PTM MAIT cells were activated and exhibited a loss of Tbet expression but were not depleted as in HIV infection. Our data suggest the following: 1) MAIT cell activation and exhaustion is uncoupled from the hallmark depletion of MAIT cells during HIV infection; and 2) the lack of PTM MAIT cell enrichment at the gut mucosa may prevent depletion during chronic infection, providing a model to assess potential immunotherapeutic approaches to modify MAIT cell trafficking during HIV infection.

AB - Mucosal-associated invariant T (MAIT) cells are nonconventional T lymphocytes that recognize bacterial metabolites presented by MR1. Whereas gut bacterial translocation and the loss/dysfunction of peripheral MAIT cells in HIV infection is well described, MAIT cells in nonhuman primate models are poorly characterized.We generated a pigtail macaque (PTM)-specific MR1 tetramer and characterized MAIT cells in serial samples from naive and SIV- or simian HIV-infected PTM. Although PTM MAIT cells generally resemble the phenotype and transcriptional profile of human MAIT cells, they exhibited uniquely low expression of the gut-homing marker α4β7 and were not enriched at the gut mucosa. PTM MAIT cells responded to SIV/simian HIV infection by proliferating and upregulating α4β7, coinciding with increased MAIT cell frequency in the rectum. By 36 wk of infection, PTM MAIT cells were activated and exhibited a loss of Tbet expression but were not depleted as in HIV infection. Our data suggest the following: 1) MAIT cell activation and exhaustion is uncoupled from the hallmark depletion of MAIT cells during HIV infection; and 2) the lack of PTM MAIT cell enrichment at the gut mucosa may prevent depletion during chronic infection, providing a model to assess potential immunotherapeutic approaches to modify MAIT cell trafficking during HIV infection.

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M3 - Article

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JF - Journal of Immunology

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