scholarly journals Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19

2020 ◽  
Author(s):  
Chen Yu ◽  
Sejiro Littleton ◽  
Nicholas Giroux ◽  
Rose Mathew ◽  
Shengli Ding ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Gene Signature ◽  
Peripheral Blood Mononuclear ◽  
Color Flow ◽  
Sexual Dimorphisms ◽  
Mait Cells ◽  
Cell Responses ◽  
Female Specific ◽  
Pronounced Reduction ◽  
Mait Cell

ABSTRACTSexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, yet the mechanisms governing this disparity remain incompletely understood. We carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36-color flow cytometry and single cell RNA-sequencing. Our results revealed a pronounced reduction of circulating mucosal associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets implicate that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, female MAIT cells possessed an immunologically active gene signature, whereas male counterparts were pro-apoptotic. Collectively, our findings uncover a female-specific protective MAIT profile, potentially shedding light on reduced COVID-19 susceptibility in females.

Altered distribution and enhanced osteoclastogenesis of mucosal-associated invariant T cells in gouty arthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (8) ◽  
pp. 2124-2134
Author(s):  
Young-Nan Cho ◽  
Hae-Seong Jeong ◽  
Ki-Jeong Park ◽  
Hyung-Seok Kim ◽  
Eun-Hee Kim ◽  
...  
Keyword(s):  
Cell Activation ◽  
Mononuclear Cells ◽  
Gouty Arthritis ◽  
Bone Destruction ◽  
Peripheral Blood Mononuclear ◽  
Mait Cells ◽  
Tnf Α ◽  
Mait Cell ◽  
Msu Crystals

Abstract Objective This study was designed to investigate the role of mucosal-associated invariant T (MAIT) cells in gouty arthritis (GA) and their effects on osteoclastogenesis. Methods Patients with GA (n = 61), subjects with hyperuricaemia (n = 11) and healthy controls (n = 30) were enrolled in this study. MAIT cells, cytokines, CD69, programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells in the presence of M-CSF and RANK ligand. Results Circulating MAIT cell levels were significantly reduced in GA patients. However, their capacities for IFN-γ, IL-17 and TNF-α production were preserved. Expression levels of CD69, PD-1 and LAG-3 in MAIT cells were found to be elevated in GA patients. In particular, CD69 expression in circulating MAIT cells was increased by stimulation with MSU crystals, suggesting that deposition of MSU crystals might contribute to MAIT cell activation. Interestingly, MAIT cells were found to be accumulated in synovial fluid and infiltrated into gouty tophus tissues within joints. Furthermore, activated MAIT cells secreted pro-resorptive cytokines (i.e. IL-6, IL-17 and TNF-α) and facilitated osteoclastogenesis. Conclusion This study demonstrates that circulating MAIT cells are activated and numerically deficient in GA patients. In addition, MAIT cells have the potential to migrate to inflamed tissues and induce osteoclastogenesis. These findings provide an important role of MAIT cells in the pathogenesis of inflammation and bone destruction in GA patients.

scholarly journals Clostridioides difficile Toxin CDT Induces Cytotoxic Responses in Human Mucosal-Associated Invariant T (MAIT) Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Isabel Marquardt ◽  
Josefine Jakob ◽  
Jessica Scheibel ◽  
Julia Danielle Hofmann ◽  
Frank Klawonn ◽  
...  
Keyword(s):  
Cell Activation ◽  
Binary Toxin ◽  
Peripheral Blood Mononuclear ◽  
Host Immune Responses ◽  
Mait Cells ◽  
Cell Responses ◽  
Clostridioides Difficile ◽  
Lytic Granule ◽  
Mait Cell

Clostridioides difficile is the major cause of antibiotic-associated colitis (CDAC) with increasing prevalence in morbidity and mortality. Severity of CDAC has been attributed to hypervirulent C. difficile strains, which in addition to toxin A and B (TcdA, TcdB) produce the binary toxin C. difficile transferase (CDT). However, the link between these toxins and host immune responses as potential drivers of immunopathology are still incompletely understood. Here, we provide first experimental evidence that C. difficile toxins efficiently activate human mucosal-associated invariant T (MAIT) cells. Among the tested toxins, CDT and more specifically, the substrate binding and pore-forming subunit CDTb provoked significant MAIT cell activation resulting in selective MAIT cell degranulation of the lytic granule components perforin and granzyme B. CDT-induced MAIT cell responses required accessory immune cells, and we suggest monocytes as a potential CDT target cell population. Within the peripheral blood mononuclear cell fraction, we found increased IL-18 levels following CDT stimulation and MAIT cell response was indeed partly dependent on this cytokine. Surprisingly, CDT-induced MAIT cell activation was found to be partially MR1-dependent, although bacterial-derived metabolite antigens were absent. However, the role of antigen presentation in this process was not analyzed here and needs to be validated in future studies. Thus, MR1-dependent induction of MAIT cell cytotoxicity might be instrumental for hypervirulent C. difficile to overcome cellular barriers and may contribute to pathophysiology of CDAC.

scholarly journals Frequencies of CD8 and DN MAIT Cells Among Children Diagnosed With Type 1 Diabetes Are Similar to Age-Matched Controls

2021 ◽  
Vol 12 ◽  
Author(s):  
Robert Z. Harms ◽  
Katie R. Ostlund ◽  
Monina Cabrera ◽  
Earline Edwards ◽  
Victoria B. Smith ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Mononuclear Cells ◽  
Cell Frequency ◽  
Extrinsic Factors ◽  
Peripheral Blood Mononuclear ◽  
Mait Cells ◽  
25 Oh Vitamin D ◽  
Mait Cell

Mucosal-associated invariant T (MAIT) cells have been implicated in various forms of autoimmunity, including type 1 diabetes (T1D). Here, we tested the hypothesis that CD8 and double negative (DN) MAIT cell frequencies were altered among diagnosed T1D subjects compared to controls. To do this, we analyzed cryopreserved peripheral blood mononuclear cells (PBMCs) from age-matched T1D and control children using flow cytometry. We observed that CD8 and DN MAIT cell frequencies were similarly abundant between the two groups. We tested for associations between MAIT cell frequency and T1D-associated parameters, which could reveal a pathogenic role for MAIT cells in the absence of changes in frequency. We found no significant associations between CD8 and DN MAIT cell frequency and levels of islet cell autoantibodies (ICA), glutamate decarboxylase 65 (GAD65) autoantibodies, zinc transporter 8 (ZNT8) autoantibodies, and insulinoma antigen 2 (IA-2) autoantibodies. Furthermore, CD8 and DN MAIT cell frequencies were not significantly associated with time since diagnosis, c-peptide levels, HbA1c, and BMI. As we have examined this cohort for multiple soluble factors previously, we tested for associations between relevant factors and MAIT cell frequency. These could help to explain the broad range of MAIT frequencies we observed and/or indicate disease-associated processes. Although we found nothing disease-specific, we observed that levels of IL-7, IL-18, 25 (OH) vitamin D, and the ratio of vitamin D binding protein to 25 (OH) vitamin D were all associated with MAIT cell frequency. Finally, previous cytomegalovirus infection was associated with reduced CD8 and DN MAIT cells. From this evaluation, we found no connections between CD8 and DN MAIT cells and children with T1D. However, we did observe several intrinsic and extrinsic factors that could influence peripheral MAIT cell abundance among all children. These factors may be worth consideration in future experimental design.

scholarly journals MAIT cells regulate NK cell-mediated tumor immunity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Emma V. Petley ◽  
Hui-Fern Koay ◽  
Melissa A. Henderson ◽  
Kevin Sek ◽  
Kirsten L. Todd ◽  
...  
Keyword(s):  
Nk Cells ◽  
Tumor Immunity ◽  
Nk Cell ◽  
Prognostic Significance ◽  
Human Tumor ◽  
Gene Signature ◽  
Mouse Tumor ◽  
Mait Cells ◽  
Mait Cell

AbstractThe function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment.

scholarly journals Analysis of CD4+ T-Cell Responses to Human Papillomavirus (HPV) Type 11 L1 in Healthy Adults Reveals a High Degree of Responsiveness and Cross-Reactivity with Other HPV Types

2002 ◽  
Vol 76 (15) ◽  
pp. 7418-7429 ◽  
Author(s):  
O. Martin Williams ◽  
Keith W. Hart ◽  
Eddie C. Y. Wang ◽  
Colin M. Gelder
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
In Vitro Selection ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
Peripheral Blood Mononuclear ◽  
Cell Responses ◽  
Hpv Types

ABSTRACT Human papillomavirus type 11 (HPV-11) infection causes genital warts and recurrent respiratory papillomatosis. While there is compelling evidence that CD4+ T cells play an important role in immune surveillance of HPV-associated diseases, little is known about human CD4+ T-cell recognition of HPV-11. We have investigated the CD4+ T-cell responses of 25 unrelated healthy donors to HPV-11 L1 virus-like particles (VLP). CD4+ T-cell lines from 21 of 25 donors were established. Cell sorting experiments carried out on cells from six donors demonstrated that the response was located in the CD45RAlow CD45ROhigh memory T-cell population. To determine the peptide specificity of these responses, epitope selection was analyzed by using 95 15-mer peptides spanning the entire HPV-11 L1 protein. No single region of L1 was immunodominant; responders recognized between 1 and 10 peptides, located throughout the protein, and peptide responses fell into clear HLA class II restricted patterns. Panels of L1 peptides specific for skin and genital HPV were used to show that the L1 CD4+ T-cell responses were cross-reactive. The degree of cross-reactivity was inversely related to the degree of L1 sequence diversity between these viruses. Finally, responses to HPV-11 L1 peptides were elicited from ex vivo CD45RO+ peripheral blood mononuclear cells, demonstrating that recognition of HPV-11 was a specific memory response and not due to in vitro selection during tissue culture. This is the first study of CD4+ T-cell responses to HPV-11 in healthy subjects and demonstrates marked cross-reactivity with other skin and genital HPV types. This cross-reactivity may be of significance for vaccine strategies against HPV-associated clinical diseases.

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