Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/136874
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Type: | Journal article |
Title: | Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium |
Author: | Murray-Brown, W. Guo, Y. Small, A. Lowe, K. Weedon, H. Smith, M.D. Lester, S.E. Proudman, S.M. Rao, N.L. Hao, L.-Y. Nagpal, S. Wechalekar, M.D. |
Citation: | RMD Open, 2022; 8(2):1-7 |
Publisher: | BMJ |
Issue Date: | 2022 |
ISSN: | 2056-5933 2056-5933 |
Statement of Responsibility: | William Murray-Brown, Yanxia Guo, Annabelle Small, Katie Lowe, Helen Weedon, Malcolm D Smith, Susan E Lester, Susanna M Proudman, Navin L Rao, Ling-Yang Hao, Sunil Nagpal, Mihir D Wechalekar |
Abstract: | Objectives: Programmed cell death protein 1 (PD-1)- expressing T cells are implicated in the pathogenesis of autoimmune inflammatory diseases such as rheumatoid arthritis. A subset of CXCR5− T cells, termed T peripheral helper (Tph) cells, which drive B cell differentiation, have been identified in ectopic lymphoid structures in established rheumatoid arthritis synovial tissue. Here, we aimed to characterise these in treatment-naïve, early rheumatoid arthritis to determine whether these cells accumulate prior to fully established disease. Methods: Fresh dissociated tissue and peripheral blood mononuclear cell (PBMC) suspensions were stained with Zombie UV, followed by anti-CD45RO, PD-1, CD3, ICOS, CD8, CD4, CD20, CXCR5, TIGIT and CD38 antibodies prior to analysis. For histology, rheumatoid arthritis synovial sections were prepared for Opal multispectral immunofluorescence with anti-CD45RO, CD20, PD-1 and CXCR5 antibodies. Images were acquired on the Perkin Elmer Vectra V.3.0 imaging system and analysed using InForm Advanced Image Analysis software. Results: Flow cytometry revealed T cell infiltration in the rheumatoid arthritis synovium with differential expression of PD-1, CD45RO, ICOS, TIGIT and CD38. We observed a higher frequency of PD1hiCXCR5− Tph in rheumatoid arthritis synovial tissue and PBMCs versus controls, and no significant difference in T follicular helper cell frequency. Microscopy identified a 10-fold increase of Tph cells in early rheumatoid arthritis synovial follicular and diffuse regions, and identified Tph adjacent to germinal centre B cells. Conclusions: These data demonstrate that PD-1hi Tph cells are present in early rheumatoid arthritis, but not osteoarthritis synovium, and therefore may provide a target for treatment of patients with early rheumatoid arthritis. |
Keywords: | Rheumatoid Arthritis |
Rights: | © Author(s) (or their employer(s)) 2022.This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/ licenses/by/4.0/. |
DOI: | 10.1136/rmdopen-2022-002563 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/2004839 |
Published version: | http://dx.doi.org/10.1136/rmdopen-2022-002563 |
Appears in Collections: | Medicine publications |
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File | Description | Size | Format | |
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hdl_136874.pdf | Published version | 6.13 MB | Adobe PDF | View/Open |
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