Loss of Circulating Mucosal-Associated Invariant T Cells in Common Variable Immunodeficiency Is Associated with Immune Activation and Loss of Eomes and PLZF

Paquin‐Proulx, Dominic; Santos, Bianca A. N.; Barsotti, Nathália Silveira; Marinho, Ana Karolina Barreto Berselli; Kokron, Cristina Maria; Carvalho, Karina I.; Barros, Myrthes Toledo; Kalil, Jorge; Elmacken, Mona; Sandberg, Johan K.; Kallás, Esper G.; Nixon, Douglas F.

doi:10.4049/immunohorizons.1700039

Cited by 8 publications

(7 citation statements)

References 55 publications

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“…In chronic HIV-1 and HTLV-1 infections, MAIT cells are reduced in number and display impaired functionality in response to bacterial stimulation[ 19 – 21 ]. A similar MAIT cell impairement has been described in patients with chronic infections due to a primary immunodeficiency[ 22 ].…”

Section: Introductionsupporting

confidence: 55%

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection

et al. 2018

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Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

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Section: Introductionsupporting

confidence: 55%

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection

et al. 2018

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“…The remaining MAIT cells reflected a different cytokine-producing pattern with significantly much more secretion of TNFα, IL-17A, and IL-22 than the control subjects, also they showed significantly higher expression of lymphocyte activation hallmarks including CD69, CD38, and HLA-DR but in contrast lower expression of CCR6 indicative of more highly activated MAIT cells in CVID patients compared with healthy controls. They also displayed a poor IFNγ response upon in vitro stimulation by Escherichia coli 189,193. A similar pattern has been demonstrated in chronic bacterial or viral infections such as infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) that might explain such alike situation in CVID patients 194.…”

supporting

confidence: 55%

Role of rare immune cells in common variable immunodeficiency

Soltani

Rezaei

Fekrvand

et al. 2022

Pediatric Allergy Immunology

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Common variable immunodeficiency disorder (CVID) is the most frequent symptomatic inborn errors of immunity (IEIs) 1 with an estimated prevalence of 1:50,000-1:25,000. 2 CVID is characterized by hypogammaglobulinemia, impaired production of specific immunoglobulin (Ig), and increased susceptibility to recurrent infections. Clinical manifestations in CVID patients demonstrate a wide spectrum of complications including recurrent infections, pulmonary complications, granulomatous or polyclonal lymphocytic infiltrations, autoimmunity, gastrointestinal diseases, and neoplasia, which can be established in different periods of life, from childhood to late adulthood. 3,4 Immunoglobulin replacement therapy is the most important therapeutic intervention for decreasing chronic infections and infectious sequels of these patients. 5

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“…However, only four patients were analyzed, one of which had a normal number of MAIT cells. A study of common variable immunodeficiency (CVID) provides indirect evidence against a role for B cells in regulating human MAIT cell frequency ( 159 ). Although the abundance of B cells and MAIT cells was variably decreased in CVID patients, the frequency of MAIT cells showed no correlation with that of B cells.…”

Section: Developmentmentioning

confidence: 99%

Insights Into Mucosal-Associated Invariant T Cell Biology From Studies of Invariant Natural Killer T Cells

2018

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Mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells are innate-like T cells that function at the interface between innate and adaptive immunity. They express semi-invariant T cell receptors (TCRs) and recognize unconventional non-peptide ligands bound to the MHC Class I-like molecules MR1 and CD1d, respectively. MAIT cells and iNKT cells exhibit an effector-memory phenotype and are enriched within the liver and at mucosal sites. In humans, MAIT cell frequencies dwarf those of iNKT cells, while in laboratory mouse strains the opposite is true. Upon activation via TCR- or cytokine-dependent pathways, MAIT cells and iNKT cells rapidly produce cytokines and show direct cytotoxic activity. Consequently, they are essential for effective immunity, and alterations in their frequency and function are associated with numerous infectious, inflammatory, and malignant diseases. Due to their abundance in mice and the earlier development of reagents, iNKT cells have been more extensively studied than MAIT cells. This has led to the routine use of iNKT cells as a reference population for the study of MAIT cells, and such an approach has proven very fruitful. However, MAIT cells and iNKT cells show important phenotypic, functional, and developmental differences that are often overlooked. With the recent availability of new tools, most importantly MR1 tetramers, it is now possible to directly study MAIT cells to understand their biology. Therefore, it is timely to compare the phenotype, development, and function of MAIT cells and iNKT cells. In this review, we highlight key areas where MAIT cells show similarity or difference to iNKT cells. In addition, we discuss important avenues for future research within the MAIT cell field, especially where comparison to iNKT cells has proven less informative.

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Loss of Circulating Mucosal-Associated Invariant T Cells in Common Variable Immunodeficiency Is Associated with Immune Activation and Loss of Eomes and PLZF

Cited by 8 publications

References 55 publications

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection

Role of rare immune cells in common variable immunodeficiency

Insights Into Mucosal-Associated Invariant T Cell Biology From Studies of Invariant Natural Killer T Cells

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