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CD8⁺ T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.

ABSTRACT: CD8⁺ T cells are cytotoxic lymphocytes that destroy pathogen infected and malignant cells through release of cytolytic molecules and proinflammatory cytokines. Although the role of CD8⁺ T cells in connective tissue diseases (CTDs) has not been explored as thoroughly as that of other immune cells, research focusing on this key component of the immune system has recently gained momentum. Aberrations in cytotoxic cell function may have implications in triggering autoimmunity and may promote tissue damage leading to exacerbation of disease. In this comprehensive review of current literature, we examine the role of CD8⁺ T cells in systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, polymyositis, and dermatomyositis with specific focus on comparing what is known about CD8⁺ T cell peripheral blood phenotypes, CD8⁺ T cell function, and CD8⁺ T cell organ-specific profiles in adult and juvenile forms of these disorders. Although, the precise role of CD8⁺ T cells in the initiation of autoimmunity and disease progression remains to be elucidated, increasing evidence indicates that CD8⁺ T cells are emerging as an attractive target for therapy in CTDs.

SUBMITTER: Radziszewska A

PROVIDER: S-EPMC9569696 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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CD8+ T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.

Radziszewska Anna A Moulder Zachary Z Jury Elizabeth C EC Ciurtin Coziana C

International journal of molecular sciences 20220928 19

CD8+ T cells are cytotoxic lymphocytes that destroy pathogen infected and malignant cells through release of cytolytic molecules and proinflammatory cytokines. Although the role of CD8+ T cells in connective tissue diseases (CTDs) has not been explored as thoroughly as that of other immune cells, research focusing on this key component of the immune system has recently gained momentum. Aberrations in cytotoxic cell function may have implications in triggering autoimmunity a ...[more]

PMID: 36232733

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Project description:PurposeTo determine the reliability and repeatability of quantitative evaluation of areas of decreased autofluorescence (DAF) from fundus autofluorescence (FAF) images and track disease progression in children with Stargardt disease (STGD1), and to investigate clinical and genotype correlations, disease symmetry, and intrafamilial variability.DesignProspective cohort study.MethodsChildren and adults with molecularly confirmed STGD1 (n = 90) underwent longitudinal FAF imaging with subsequent semiautomated measurement of the area of DAF and calculation of the annual rate of progression. The age of disease onset was recorded for all subjects, as well as the electroretinography (ERG) group at baseline (n = 86). Patients were grouped for analysis based on the age at baseline and age of onset, into children (n = 56), adults with childhood-onset STGD1 (n = 15), and adults with adult-onset (n = 19). Fifty FAF images were selected randomly and analyzed by 2 observers to evaluate repeatability and reproducibility. Differences between groups, interocular symmetry, genotype-phenotype correlations, and intrafamilial variability were also investigated both for baseline measurements as well as progression rates. We measured visual acuity, molecular genetics, ERG group, FAF metrics, and their correlations.ResultsThe mean age of onset ± SD was 9.6 ± 3.4 years for childhood-onset (n = 71) and 28.3 ± 7.8 years for adult-onset STGD1 (n = 19). The intra- and interobserver reliability of DAF quantification was excellent (intraclass correlation coefficients 0.995 and 0.987, respectively). DAF area was symmetric between eyes and the mean rate of progression (SD) was 0.69 (0.72), 0.78 (0.48), and 0.40 (0.36) mm2/year for children, adults with childhood-onset, and adults with adult-onset disease, respectively. Patients belonging to a group 3 ERG phenotype (generalized cone and rod dysfunction) had a significantly greater progression rate. Limited intrafamilial variability was observed.ConclusionsThis is the first large prospective study of FAF in a cohort of molecularly confirmed children with STGD1. DAF area quantification was highly reliable and may thereby serve as a robust structural endpoint. A high rate of progression was observed in childhood-onset disease, making this subtype of STGD1 ideally suited to be considered for prioritization in clinical trials.

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CD8⁺ T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.

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CD8<sup>+</sup> T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.

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Dataset Information

CD8+ T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.

Publications

CD8&lt;sup&gt;+&lt;/sup&gt; T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.

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OmicsDI is part of the ELIXIR infrastructure

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CD8⁺ T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.

CD8<sup>+</sup> T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.