Increased Frequency of CD4<sup>+</sup> Follicular Helper T and CD8<sup>+</sup> Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis
Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles i...
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MDPI AG
2022-03-01
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| author | Dornatien Chuo Anang Tamara H. Ramwadhdoebe Janine S. Hähnlein Bo van Kuijk Noortje Smits Krijn P. van Lienden Mario Maas Daniëlle M. Gerlag Paul P. Tak Niek de Vries Lisa G. M. van Baarsen |
| author_facet | Dornatien Chuo Anang Tamara H. Ramwadhdoebe Janine S. Hähnlein Bo van Kuijk Noortje Smits Krijn P. van Lienden Mario Maas Daniëlle M. Gerlag Paul P. Tak Niek de Vries Lisa G. M. van Baarsen |
| author_sort | Dornatien Chuo Anang |
| collection | DOAJ |
| description | Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody-positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Subsequently, we confirmed their presence in lymph nodes and synovial tissue of RA patients using immunofluorescence microscopy. In the blood, the frequency of Tfh cells did not differ between study groups. In lymphoid and synovial tissues, Tfh cells were localized in B-cell areas, and their frequency correlated with the frequency of CD19<sup>+</sup> B cells. Compared to lymphoid tissues of healthy controls, those of RA patients and RA-risk individuals showed more CD19<sup>+</sup> B cells, CD4<sup>+</sup>CXCR5<sup>+</sup> follicular helper T cells, and CD8<sup>+</sup>CXCR5<sup>+</sup> follicular T cells. These Tfh cells produced less IL-21 upon ex vivo stimulation. These findings suggest that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of RA to prevent further disease progression. |
| first_indexed | 2024-03-09T12:01:10Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T12:01:10Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-e38b906e9461465c996a344d9fd2414a2023-11-30T23:03:32ZengMDPI AGCells2073-44092022-03-01117110410.3390/cells11071104Increased Frequency of CD4<sup>+</sup> Follicular Helper T and CD8<sup>+</sup> Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid ArthritisDornatien Chuo Anang0Tamara H. Ramwadhdoebe1Janine S. Hähnlein2Bo van Kuijk3Noortje Smits4Krijn P. van Lienden5Mario Maas6Daniëlle M. Gerlag7Paul P. Tak8Niek de Vries9Lisa G. M. van Baarsen10Amsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsAmsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsAmsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsAmsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsAmsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsDepartment of Radiology, Amsterdam UMC, University of Amsterdam, 1007 MB Amsterdam, The NetherlandsDepartment of Radiology, Amsterdam UMC, University of Amsterdam, 1007 MB Amsterdam, The NetherlandsAmsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsAmsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsAmsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsAmsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, 1007 MB Amsterdam, The NetherlandsFollicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody-positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Subsequently, we confirmed their presence in lymph nodes and synovial tissue of RA patients using immunofluorescence microscopy. In the blood, the frequency of Tfh cells did not differ between study groups. In lymphoid and synovial tissues, Tfh cells were localized in B-cell areas, and their frequency correlated with the frequency of CD19<sup>+</sup> B cells. Compared to lymphoid tissues of healthy controls, those of RA patients and RA-risk individuals showed more CD19<sup>+</sup> B cells, CD4<sup>+</sup>CXCR5<sup>+</sup> follicular helper T cells, and CD8<sup>+</sup>CXCR5<sup>+</sup> follicular T cells. These Tfh cells produced less IL-21 upon ex vivo stimulation. These findings suggest that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of RA to prevent further disease progression.https://www.mdpi.com/2073-4409/11/7/1104rheumatoid arthritislymph nodesT lymphocytesB lymphocytesfollicular T helper cells |
| spellingShingle | Dornatien Chuo Anang Tamara H. Ramwadhdoebe Janine S. Hähnlein Bo van Kuijk Noortje Smits Krijn P. van Lienden Mario Maas Daniëlle M. Gerlag Paul P. Tak Niek de Vries Lisa G. M. van Baarsen Increased Frequency of CD4<sup>+</sup> Follicular Helper T and CD8<sup>+</sup> Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis Cells rheumatoid arthritis lymph nodes T lymphocytes B lymphocytes follicular T helper cells |
| title | Increased Frequency of CD4<sup>+</sup> Follicular Helper T and CD8<sup>+</sup> Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis |
| title_full | Increased Frequency of CD4<sup>+</sup> Follicular Helper T and CD8<sup>+</sup> Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis |
| title_fullStr | Increased Frequency of CD4<sup>+</sup> Follicular Helper T and CD8<sup>+</sup> Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis |
| title_full_unstemmed | Increased Frequency of CD4<sup>+</sup> Follicular Helper T and CD8<sup>+</sup> Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis |
| title_short | Increased Frequency of CD4<sup>+</sup> Follicular Helper T and CD8<sup>+</sup> Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis |
| title_sort | increased frequency of cd4 sup sup follicular helper t and cd8 sup sup follicular t cells in human lymph node biopsies during the earliest stages of rheumatoid arthritis |
| topic | rheumatoid arthritis lymph nodes T lymphocytes B lymphocytes follicular T helper cells |
| url | https://www.mdpi.com/2073-4409/11/7/1104 |
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