Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium
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 ec...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022-10-01
|
| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/8/2/e002563.full |
| _version_ | 1811257476119527424 |
|---|---|
| author | Susanna M Proudman Ling-Yang Hao William Murray-Brown Helen Weedon Malcolm D Smith Mihir D Wechalekar Susan E Lester Sunil Nagpal Yanxia Guo Annabelle Small Katie Lowe Navin L Rao |
| author_facet | Susanna M Proudman Ling-Yang Hao William Murray-Brown Helen Weedon Malcolm D Smith Mihir D Wechalekar Susan E Lester Sunil Nagpal Yanxia Guo Annabelle Small Katie Lowe Navin L Rao |
| author_sort | Susanna M Proudman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T17:57:04Z |
| format | Article |
| id | doaj.art-f7fc10303c3b466ab3977cd24072ecdf |
| institution | Directory Open Access Journal |
| issn | 2056-5933 |
| language | English |
| last_indexed | 2024-04-12T17:57:04Z |
| publishDate | 2022-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj.art-f7fc10303c3b466ab3977cd24072ecdf2022-12-22T03:22:18ZengBMJ Publishing GroupRMD Open2056-59332022-10-018210.1136/rmdopen-2022-002563Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synoviumSusanna M Proudman0Ling-Yang Hao1William Murray-Brown2Helen Weedon3Malcolm D Smith4Mihir D Wechalekar5Susan E Lester6Sunil Nagpal7Yanxia Guo8Annabelle Small9Katie Lowe10Navin L Rao11Department of Rheumatology, Royal Adelaide Hospital, Adelaide, Victoria, AustraliaAff1 grid.476494.cLycera Corp. Ann Arbor MI USACollege of Medicine & Public Health, Flinders University, Adelaide, South Australia, AustraliaCollege of Medicine & Public Health, Flinders University, Adelaide, South Australia, AustraliaCollege of Medicine & Public Health, Flinders University, Adelaide, South Australia, AustraliaCollege of Medicine & Public Health, Flinders University, Adelaide, South Australia, Australia1Rheumatology Unit, The Queen Elizabeth Hospital, Woodville, South Australia4Immunology, Janssen R&D, Spring House PA, USADiscovery Immunology, Janssen Research and Development, Spring House, Pennsylvania, USADepartment of Rheumatology, Flinders University, Bedford Park, South Australia, AustraliaDepartment of Rheumatology, Flinders University, Bedford Park, South Australia, AustraliaDiscovery Immunology, Janssen Research and Development, Spring House, Pennsylvania, USAObjectives 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.https://rmdopen.bmj.com/content/8/2/e002563.full |
| spellingShingle | Susanna M Proudman Ling-Yang Hao William Murray-Brown Helen Weedon Malcolm D Smith Mihir D Wechalekar Susan E Lester Sunil Nagpal Yanxia Guo Annabelle Small Katie Lowe Navin L Rao Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium RMD Open |
| title | Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium |
| title_full | Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium |
| title_fullStr | Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium |
| title_full_unstemmed | Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium |
| title_short | Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium |
| title_sort | differential expansion of t peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium |
| url | https://rmdopen.bmj.com/content/8/2/e002563.full |
| work_keys_str_mv | AT susannamproudman differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT lingyanghao differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT williammurraybrown differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT helenweedon differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT malcolmdsmith differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT mihirdwechalekar differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT susanelester differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT sunilnagpal differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT yanxiaguo differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT annabellesmall differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT katielowe differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium AT navinlrao differentialexpansionoftperipheralhelpercellsinearlyrheumatoidarthritisandosteoarthritissynovium |