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; Amarasena, Thakshila; Meehan, Bronwyn S.; Mak, Jeffrey Y. W.; Liu, Ligong; Fairlie, David P.; McCluskey, James; Eckle, Sidonia B G; Kent, Stephen J.

doi:10.4049/jimmunol.1801405

Cited by 35 publications

(82 citation statements)

References 52 publications

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“…IFN-γ producing capacity was maintained, suggesting that there is a restoration of IFN-γ-producing MAIT cells in the blood ( Figure 3E). Recently, it has been shown that MAIT cells upregulate α4β7 (the gut homing integrin) during SIV infection in pigtail macaques (24); hence, we looked at the expression of α4β7 on RM blood MAIT cells during SHIV infection. Similar to the data on pigtail macaques, the expression of gut homing marker α4β7 was significantly higher on RM MAIT cells compared to non-MAIT cells post-SHIV infection ( Figure 3F).…”

Section: Mait Cells In Shiv-infected Macaques Are Highly Proliferativmentioning

confidence: 99%

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Functional MAIT Cells Are Associated With Reduced Simian–Human Immunodeficiency Virus Infection

et al. 2020

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Section: Mait Cells In Shiv-infected Macaques Are Highly Proliferativmentioning

confidence: 99%

“…Similarly, MAIT cells have been shown to be reduced systemically in SIV-infected rhesus macaques (23). However, a recent study in SIV/SHIV-infected pigtail macaque, MAIT cells are shown to be increased in the blood (24). Results from these studies vary, and very few studies have been performed in rhesus macaques with SIV/SHIV infection.…”

Section: Introductionmentioning

confidence: 99%

Functional MAIT Cells Are Associated With Reduced Simian–Human Immunodeficiency Virus Infection

et al. 2020

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“…Thus, it is reasonable to assume that human MR1 tetramers can be used to characterize MAIT cells in other species. Nonetheless, species‐specific MR1 tetramers have been developed at least for mouse (Chen et al., ; Rahimpour et al., ) and macaque (Greene et al., ; Juno et al., ), and these represent superior reagents for analysis of MAIT cells in their respective species. Techniques described in this article are in part transferrable to studying macaque MAIT cells (Juno et al., ).…”

Section: Commentarymentioning

confidence: 99%

“…Nonetheless, species‐specific MR1 tetramers have been developed at least for mouse (Chen et al., ; Rahimpour et al., ) and macaque (Greene et al., ; Juno et al., ), and these represent superior reagents for analysis of MAIT cells in their respective species. Techniques described in this article are in part transferrable to studying macaque MAIT cells (Juno et al., ). Mouse models of disease have proven valuable for definitively assessing the role of MAIT cells in disease, described as part of Chen et al ().…”

Section: Commentarymentioning

confidence: 99%

Characterization of Human Mucosal‐associated Invariant T (MAIT) Cells

Souter

Loh

et al. 2019

CP in Immunology

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Mucosal‐associated invariant T (MAIT) cells are a subset of unconventional T cells restricted by the major histocompatibility complex (MHC) class I–like molecule MHC‐related protein 1 (MR1). MAIT cells are found throughout the body, especially in human blood and liver. Unlike conventional T cells, which are stimulated by peptide antigens presented by MHC molecules, MAIT cells recognize metabolite antigens derived from an intermediate in the microbial biosynthesis of riboflavin. MAIT cells mediate protective immunity to infections by riboflavin‐producing microbes via the production of cytokines and cytotoxicity. The discovery of stimulating MAIT cell antigens allowed for the development of an analytical tool, the MR1 tetramer, that binds specifically to the MAIT T cell receptor (TCR) and is becoming the gold standard for identification of MAIT cells by flow cytometry. This article describes protocols to characterize the phenotype of human MAIT cells in blood and tissues by flow cytometry using fluorescently labeled human MR1 tetramers alongside antibodies specific for MAIT cell markers. © 2019 by John Wiley & Sons, Inc. The main protocols include: Basic Protocol 1: Determining the frequency and steady‐state surface phenotype of human MAIT cells Basic Protocol 2: Determining the activation phenotype of human MAIT cells in blood Basic Protocol 3: Characterizing MAIT cell TCRs using TCR‐positive reporter cell lines Alternate protocols are provided for determining the absolute number, transcription factor phenotype, and TCR usage of human MAIT cells; and determining activation phenotype by staining for intracellular markers, measuring secreted cytokines, and measuring fluorescent dye dilution due to proliferation. Additional methods are provided for determining the capacity of MAIT cells to produce cytokine independently of antigen using plate‐bound or bead‐immobilized CD3/CD28 stimulation; and determining the MR1‐Ag dependence of MAIT cell activation using MR1‐blocking antibody or competitive inhibition. For TCR‐positive reporter cell lines, methods are also provided for evaluating the MAIT TCR‐mediated MR1‐Ag response, determining the capacity of the reporter lines to produce cytokine independently of antigen, determining the MR1‐Ag dependence of the reporter lines, and evaluating the MR1‐Ag response of the reporter lines using IL‐2 secretion. Support Protocols describe the preparation of PBMCs from human blood, the preparation of single‐cell suspensions from tissue, the isolation of MAIT cells by FACS and MACS, cloning MAIT TCRα and β chain genes and MR1 genes for transduction, generating stably and transiently transfected cells lines, generating a stable MR1 knockout antigen‐presenting cell line, and generating monocyte‐derived dendritic cells.

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“…We used Mauritian cynomolgus macaques (MCM), which have simplified major histocompatibility complex (MHC) genetics, for these studies. SIV-positive or -naïve MCM were infected with a low dose of Mtb for [12][13][14][15][16][17][18][19][20] weeks. While no difference in TB disease between the two cohorts was observed at 4 weeks post-Mtb infection [ 1 8 ] , at 8 weeks the SIV co-infected macaques had significantly more granulomas than the SIVnaïve macaques [ 1 8 ] .…”

Section: Introductionmentioning

confidence: 99%

MAIT cells are minimally responsive to Mycobacterium tuberculosis within granulomas, but are functionally impaired by SIV in a macaque model of SIV and Mtb co-infection

Ellis-Connell

Balgeman

Larson

et al. 2020

Preprint

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Mucosal associated invariant T (MAIT) cells recognize and can directly destroy bacterially infected cells. While a role for MAIT cells has been suggested in several in vitro and in vivo models of M.tuberculosis (Mtb) infection, these studies have often focused on MAIT cells within the peripheral blood or are cross-sectional studies rather than longitudinal studies. The role of MAIT cells within granulomas and other sites of Mtb infection is relatively unknown. Furthermore, how HIV/SIV infection might impair MAIT cells at the sites of Mtb infection has not been determined. Using a Mauritian cynomolgus macaque (MCM) model system, we phenotyped MAIT cells in the peripheral blood and BAL prior to and during infection with SIVmac239. To characterize the role of MAIT cells within granulomas, SIV+ and -naïve MCM were infected with a low dose of Mtb for 6 weeks. MAIT cell frequency and function was examined within the peripheral blood, distal airways, as well as within Mtbaffected lymph nodes (LN) and tissues. Surprisingly, we found no evidence of MAIT cell responsiveness to Mtb within granulomas. Additionally, MAIT cells only minimally responded to mycobacterial stimulus in ex vivo functional assays. In contrast, most MAIT cell activation seemed to occur in samples with highly active SIV replication, including blood and SIV-infected LN. Finally, the ability of MAIT cells to secrete TNFα (TNF) was impaired during SIV and Mtb co-infection, indicating that the two pathogens together could have a synergistically deleterious effect on MAIT cell function. The effect of this

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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

Cited by 35 publications

References 52 publications

Functional MAIT Cells Are Associated With Reduced Simian–Human Immunodeficiency Virus Infection

Functional MAIT Cells Are Associated With Reduced Simian–Human Immunodeficiency Virus Infection

Characterization of Human Mucosal‐associated Invariant T (MAIT) Cells

MAIT cells are minimally responsive to Mycobacterium tuberculosis within granulomas, but are functionally impaired by SIV in a macaque model of SIV and Mtb co-infection

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