Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment

TNFα inhibitors have shaped the landscape of rheumatoid arthritis (RA) therapy with high clinical efficiency. However, their impact on T cell recall responses is not well-elucidated. We aimed to analyze the immune profiles of memory T cells in RA patients undergoing TNFα inhibitor Golimumab (GM) tre...

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Main Authors: Asma Khanniche, Ling Zhou, Bin Jiang, Jing Song, Yanhua Jin, Jian Yin, Shujun Wang, Ping Ji, Hao Shen, Ying Wang, Huji Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.00887/full
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author Asma Khanniche
Asma Khanniche
Ling Zhou
Bin Jiang
Jing Song
Yanhua Jin
Jian Yin
Shujun Wang
Ping Ji
Hao Shen
Ying Wang
Huji Xu
Huji Xu
Huji Xu
author_facet Asma Khanniche
Asma Khanniche
Ling Zhou
Bin Jiang
Jing Song
Yanhua Jin
Jian Yin
Shujun Wang
Ping Ji
Hao Shen
Ying Wang
Huji Xu
Huji Xu
Huji Xu
author_sort Asma Khanniche
collection DOAJ
description TNFα inhibitors have shaped the landscape of rheumatoid arthritis (RA) therapy with high clinical efficiency. However, their impact on T cell recall responses is not well-elucidated. We aimed to analyze the immune profiles of memory T cells in RA patients undergoing TNFα inhibitor Golimumab (GM) treatment. Frequencies of peripheral T cell subsets and cytokine expression profiles in memory T cells (TM) upon PMA/Ionomycine stimulation were determined by flow cytometry. Antigen-specific CD8 T cell immunity was analyzed through stimulating PBMCs with CMV-EBV-Flu (CEF) viral peptide pool and subsequent intracellular IFNγ staining. Both peripheral CD8 and CD4 T cells from GM treated patients had a shift pattern characterized by an enlarged effector TM and a reduced central TM cell population when compared to GM untreated group. An increase in the frequencies of TNFα+, IL-2+, and IL-17+ CD8 TM cells was observed whereas only TNFα+CD4 TM cells increased in GM treated patients. Moreover, GM treated patients contained more peripheral IFNγ-producing CD8 T cells specific to CEF viral peptides. Together, these results show a distinct T cell subset pattern and enhanced memory T cell immunity upon GM treatment, suggesting an immunoregulatory effect of TNF inhibitor Golimumab on peripheral memory T cell responses.
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spelling doaj.art-6e6fa17094b448c8a2eb781435cb471a2022-12-22T03:31:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00887437341Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker TreatmentAsma Khanniche0Asma Khanniche1Ling Zhou2Bin Jiang3Jing Song4Yanhua Jin5Jian Yin6Shujun Wang7Ping Ji8Hao Shen9Ying Wang10Huji Xu11Huji Xu12Huji Xu13Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Rheumatology and Immunology, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Rheumatology, Renji Hospital, Shanghai, ChinaDepartment of Rheumatology and Immunology, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Rheumatology and Immunology, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Rheumatology and Immunology, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, ChinaShanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesShanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, ChinaBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, ChinaPeking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, ChinaTNFα inhibitors have shaped the landscape of rheumatoid arthritis (RA) therapy with high clinical efficiency. However, their impact on T cell recall responses is not well-elucidated. We aimed to analyze the immune profiles of memory T cells in RA patients undergoing TNFα inhibitor Golimumab (GM) treatment. Frequencies of peripheral T cell subsets and cytokine expression profiles in memory T cells (TM) upon PMA/Ionomycine stimulation were determined by flow cytometry. Antigen-specific CD8 T cell immunity was analyzed through stimulating PBMCs with CMV-EBV-Flu (CEF) viral peptide pool and subsequent intracellular IFNγ staining. Both peripheral CD8 and CD4 T cells from GM treated patients had a shift pattern characterized by an enlarged effector TM and a reduced central TM cell population when compared to GM untreated group. An increase in the frequencies of TNFα+, IL-2+, and IL-17+ CD8 TM cells was observed whereas only TNFα+CD4 TM cells increased in GM treated patients. Moreover, GM treated patients contained more peripheral IFNγ-producing CD8 T cells specific to CEF viral peptides. Together, these results show a distinct T cell subset pattern and enhanced memory T cell immunity upon GM treatment, suggesting an immunoregulatory effect of TNF inhibitor Golimumab on peripheral memory T cell responses.https://www.frontiersin.org/article/10.3389/fimmu.2019.00887/fullrheumatoid arthritismemory T cellsantigen specificTNFα inhibitorimmune regulation
spellingShingle Asma Khanniche
Asma Khanniche
Ling Zhou
Bin Jiang
Jing Song
Yanhua Jin
Jian Yin
Shujun Wang
Ping Ji
Hao Shen
Ying Wang
Huji Xu
Huji Xu
Huji Xu
Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment
Frontiers in Immunology
rheumatoid arthritis
memory T cells
antigen specific
TNFα inhibitor
immune regulation
title Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment
title_full Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment
title_fullStr Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment
title_full_unstemmed Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment
title_short Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment
title_sort restored and enhanced memory t cell immunity in rheumatoid arthritis after tnfα blocker treatment
topic rheumatoid arthritis
memory T cells
antigen specific
TNFα inhibitor
immune regulation
url https://www.frontiersin.org/article/10.3389/fimmu.2019.00887/full
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