التفاصيل البيبلوغرافية
| العنوان: |
Uncovering the significance of expanded CD8+ large granular lymphocytes in inclusion body myositis: Insights into T cell phenotype and functional alterations, and disease severity |
| المؤلفون: |
Emily McLeish, Anuradha Sooda, Nataliya Slater, Barbara Kachigunda, Kelly Beer, Shereen Paramalingam, Phillipa J. Lamont, Abha Chopra, Frank Louis Mastaglia, Merrilee Needham, Jerome David Coudert |
| المصدر: |
Frontiers in Immunology, Vol 14 (2023) |
| بيانات النشر: |
Frontiers Media S.A., 2023. |
| سنة النشر: |
2023 |
| المجموعة: |
LCC:Immunologic diseases. Allergy |
| مصطلحات موضوعية: |
inclusion body myositis, T cell large granular lymphocytes, inhibitory natural killer receptors, KLRG1, senescence, Immunologic diseases. Allergy, RC581-607 |
| الوصف: |
IntroductionInclusion body myositis (IBM) is a progressive inflammatory myopathy characterised by skeletal muscle infiltration and myofibre invasion by CD8+ T lymphocytes. In some cases, IBM has been reported to be associated with a systemic lymphoproliferative disorder of CD8+ T cells exhibiting a highly differentiated effector phenotype known as T cell Large Granular Lymphocytic Leukemia (T-LGLL). MethodsWe investigated the incidence of a CD8+ T-LGL lymphoproliferative disorder in 85 IBM patients and an aged-matched group of 56 Healthy Controls (HC). Further, we analysed the phenotypical characteristics of the expanded T-LGLs and investigated whether their occurrence was associated with any particular HLA alleles or clinical characteristics. ResultsBlood cell analysis by flow cytometry revealed expansion of T-LGLs in 34 of the 85 (40%) IBM patients. The T cell immunophenotype of T-LGLHIGH patients was characterised by increased expression of surface molecules including CD57 and KLRG1, and to a lesser extent of CD94 and CD56 predominantly in CD8+ T cells, although we also observed modest changes in CD4+ T cells and γδ T cells. Analysis of Ki67 in CD57+ KLRG1+ T cells revealed that only a small proportion of these cells was proliferating. Comparative analysis of CD8+ and CD4+ T cells isolated from matched blood and muscle samples donated by three patients indicated a consistent pattern of more pronounced alterations in muscles, although not significant due to small sample size. In the T-LGLHIGH patient group, we found increased frequencies of perforin-producing CD8+ and CD4+ T cells that were moderately correlated to combined CD57 and KLRG1 expression. Investigation of the HLA haplotypes of 75 IBM patients identified that carriage of the HLA-C*14:02:01 allele was significantly higher in T-LGLHIGH compared to T-LGLLOW individuals. Expansion of T-LGL was not significantly associated with seropositivity patient status for anti-cytosolic 5'-nucleotidase 1A autoantibodies. Clinically, the age at disease onset and disease duration were similar in the T-LGLHIGH and T-LGLLOW patient groups. However, metadata analysis of functional alterations indicated that patients with expanded T-LGL more frequently relied on mobility aids than T-LGLLOW patients indicating greater disease severity. ConclusionAltogether, these results suggest that T-LGL expansion occurring in IBM patients is correlated with exacerbated immune dysregulation and increased disease burden. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1153789/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2023.1153789 |
| URL الوصول: |
https://doaj.org/article/5e3e14c36631443a9ddd2cb9fec9002a |
| رقم الانضمام: |
edsdoj.5e3e14c36631443a9ddd2cb9fec9002a |
| قاعدة البيانات: |
Directory of Open Access Journals |
Full Text Finder