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

ABSTRACT: 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.

SUBMITTER: Harms RZ

PROVIDER: S-EPMC7940386 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Harms Robert Z RZ Ostlund Katie R KR Cabrera Monina M Edwards Earline E Smith Victoria B VB Smith Lynette M LM Sarvetnick Nora N

Frontiers in immunology 20210223

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 abundan ...[more]

PMID: 33708202

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Project description:BackgroundOsteoarthritis (OA) is characterized by the degeneration of joint cartilage, with concomitant changes in the synovium and subchondral bone. Recently, the inflammatory response and involvement of several types of T-cells has been implicated in the development of OA. This study investigated the frequency of MR1-restricted mucosal-associated invariant T (MAIT) cells in patients with knee OA.MethodsForty-five patients recently diagnosed with knee OA and 21 age- and gender-matched healthy controls were recruited for this study. Percentages of circulating MAIT cells were assessed by flow cytometry. Plasma cytokine levels were measured using cytometric bead arrays. Associations between the percentages of MAIT cells, plasma cytokine levels, and clinical parameters of OA (erythrocyte sedimentation rate [ESR] and the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were analyzed using the Spearman correlation test.ResultsThe percentages of total, CD8αα, and CD8αβ MAIT cells were higher in patients with OA compared to healthy controls. The percentages of total and CD8αα MAIT cells were higher in patients with multi-joint OA (MOA) compared to patients with knee-only OA (KOA). Plasma IFN-γ and TNF-α levels were elevated in patients with OA compared to healthy controls, and there was a positive correlation between plasma IFN-γ levels and the percentages of total, CD8αα, and CD8αβ MAIT cells. Plasma IFN-γ and IL-17 levels were higher in patients with MOA compared to healthy controls or patients with KOA. There were positive correlations between the percentages of total and CD8αα MAIT cells and clinical parameters (ESR and WOMAC scores) in patients with OA or MOA. Binary logistic regression analysis shown the frequency of MAIT cells was associated with the risk of OA.ConclusionsMAIT cells and their subpopulations were significantly increased in patients with OA and have potential as biological markers of OA disease severity, especially in patients with MOA.

Project description:Introduction. Many children with specific language impairment (SLI) have problems with language comprehension, and little is known about how to remediate these. We focused here on errors in interpreting sentences such as "the ball is above the cup", where the spatial configuration depends on word order. We asked whether comprehension of such short reversible sentences could be improved by computerized training, and whether learning by children with SLI resembled that of younger, typically-developing children. Methods. We trained 28 children with SLI aged 6-11 years, 28 typically-developing children aged from 4 to 7 years who were matched to the SLI group for raw scores on a test of receptive grammar, and 20 typically-developing children who were matched to the SLI group on chronological age. A further 20 children with SLI were given pre- and post-test assessments, but did not undergo training. Those in the trained groups were given training on four days using a computer game adopting an errorless learning procedure, during which they had to select pictures to correspond to spoken sentences such as "the cup is above the drum" or "the bird is below the hat". Half the trained children heard sentences using above/below and the other half heard sentences using before/after (with a spatial interpretation). A total of 96 sentences was presented over four sessions. Half the sentences were unique, whereas the remainder consisted of 12 repetitions of each of four sentences that became increasingly familiar as training proceeded. Results. Age-matched control children performed near ceiling (≥ 90% correct) in the first session and were excluded from the analysis. Around half the trained SLI children also performed this well. Training effects were examined in 15 SLI and 16 grammar-matched children who scored less than 90% correct on the initial training session. Overall, children's scores improved with training. Memory span was a significant predictor of improvement, even after taking into account performance on training session 1. Unlike the grammar-matched controls, children with SLI showed greater accuracy with repeated sentences compared with unique sentences. Training did not improve children's performance on a standardized test of receptive grammar. Discussion. Overall, these results indicate that a subset of children with SLI perform well below ceiling on reversible sentences with three key words and simple syntactic structure. For these children, weak verbal short-term memory appears to impair comprehension of spoken sentences. In contrast to the general finding that rule-learning benefits from variable input, these children seem to do best if given repeated exposure to the same nouns used with a given sentence frame. Generalisation to other sentences using the same syntactic frame may be more effective if preceded by such item-specific learning.

Dataset Information

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

Publications

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

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