التفاصيل البيبلوغرافية
| العنوان: |
POS0402 CLONALLY EXPANDED CD38hi CYTOTOXIC CD8 T CELLS DEFINE THE T CELL INFILTRATE IN CHECKPOINT INHIBITOR-ASSOCIATED ARTHRITIS |
| المؤلفون: |
Wang, R., Singaraju, A., Marks, K. E., Shakib, L., Dunlap, G., Cunningham-Bussel, A., Greisen, S. R., Chen, L., Tirpack, A., Fein, M., Todd, D., Macfarlane, L., Goodman, S., Dicarlo, E., Massarotti, E., Sparks, J., Hamnvik, O. P., Min, L., Jonsson, A. H., Brenner, M., Chan, K. K., Bass, A., Donlin, L., Rao, D. |
| المصدر: |
Annals of the Rheumatic Diseases ; volume 81, issue Suppl 1, page 457.1-457 ; ISSN 0003-4967 1468-2060 |
| بيانات النشر: |
BMJ |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
General Biochemistry, Genetics and Molecular Biology, Immunology, Immunology and Allergy, Rheumatology |
| الوصف: |
Background Immune checkpoint inhibitor (ICI) therapies that promote T cell activation have improved outcomes for advanced malignancies yet can also elicit harmful autoimmune reactions. The T cell mechanisms mediating these iatrogenic autoimmune events remain unclear. Objectives To investigate the immunophenotype, transcriptomic feature and clonotypes of T cells from joints of patients affected by ICI-induced inflammatory arthritis (ICI-arthritis). Methods Detailed immunophenotyping was performed on mononuclear cells from synovial fluid (SF) using mass cytometry and flow cytometry to identify significantly altered populations in ICI-A compared to seropositive rhrumatoid arthritis (RA) and psoriatic arthritis (PsA) (p<0.05). Bulk RNA-seq was performed on altered SF CD8 T cell subsets from ICI-A, RA and PsA to investigate their transcriptomic features. Cytokine profile and pathways enriched in ICI-A CD8 T cells were examined using differentially expressed genes, intracellular staining, and in vitro culture. TCR clonotypes were examined using single cell RNA-seq of T cells from synovial fluid, tissue and blood of ICI-A. Results Compared to the autoimmune arthritides RA and PsA, ICI-arthritis joints contained an expanded CD38 hi CD127 - CD8 + T cell subset that displays cytotoxic, effector, and interferon (IFN) response signatures. Exposure of synovial T cells to Type I IFN, more so than IFN- γ , induced the CD38 hi cytotoxic phenotype. Single cell transcriptomic and T cell repertoire (TCR) analyses indicated that the abundance of CD38 hi CD8 T cells in ICI-arthritis resulted from proliferation of a limited number of clones. The CD38 hi population appeared distinct from dysfunctional T cells and clonally most related to TCF7 + memory populations. Comparison of synovial tissue from bilateral knees of the same patient demonstrated considerable sharing of TCR clonotypes among CD38 hi CD8 T cells between the two joints. Further, TCR clonotypes expanded in synovial fluid of ICI-arthritis patients were detected in ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1136/annrheumdis-2022-eular.3779 |
| الإتاحة: |
https://doi.org/10.1136/annrheumdis-2022-eular.3779Test |
| رقم الانضمام: |
edsbas.E2119DCB |
| قاعدة البيانات: |
BASE |
