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Cited by 56Rheumatoid Arthritis Research and TherapiesT-cell and B-cell ImmunologyChemokine receptors and signaling

Tissue trafficking patterns of effector memory CD4 T cells in rheumatoid arthritis.

Zhang, Xiaoyu, Nakajima, Takako, Goronzy, Jörg J., Weyand, Cornelia M.·2005·Arthritis & Rheumatism
DOI 10.1002/art.21482
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Abstract

Objective: Clonal populations of CD4+,CD28− T cells accumulating in rheumatoid arthritis functionally resemble end‐differentiated, nondividing, short‐lived effector memory cells that reside in peripheral tissues. We undertook this study to examine the tissue niche for CD4+,CD28− T cells and the signals regulating their survival and tissue homing patterns. Methods: Chemokine receptor expression on CD4+,CD28− T cell clones and peripheral blood lymphocytes was assessed by multicolor cytometry. In vitro chemotaxis and transendothelial migration were examined in a Transwell system. In vivo tissue‐homing patterns were established by adoptively transferring fluorescence‐labeled T cell clones into SCID mice engrafted either with rheumatoid synovium or with human lymph nodes. Results: CD4+,CD28− T cell clones adoptively transferred into human tissue–SCID mouse chimeras infiltrated rheumatoid synovium but preferentially homed to lymph nodes. Such T cells coexpressed the chemokine receptors CCR7, CCR5, and CXCR4 and migrated in response to both inflammatory chemokines (CCL5) and homing chemokines (CXCL12). T cell receptor crosslinking abrogated chemotactic responsiveness. In contrast, interleukin‐12 stimulation induced the up‐regulation of CCR5 and a shift in the in vivo homing pattern away from the lymph nodes toward the inflamed synovium. Conclusion: CD4+,CD28− T cells resemble both short‐lived effector memory cells and long‐lived central memory cells, and they find a niche both in inflamed synovium and in lymph nodes. Nonspecific cytokine stimulation, not antigen recognition, triggers the transition from the lymph node to the synovium. By maintaining CCR7 expression, these end‐differentiated T cells can home to lymphoid organs, enhance their survival, support clonal expansion, and perpetuate autoreactivity.

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Crossref · 10.1002/art.21482

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  • CD28− T cells produce high levels of IFN-γ, have cytotoxic functions, and accumulate in inflammatory lesions.

    “CD28− T cells are high producers for interferon-γ (IFN-γ), display cytotoxic functions and accumulate in inflammatory lesions [21–26].”

    From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [26]

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Authors
Zhang, X., Nakajima, T., Goronzy, J. J., & Weyand, C. M.
Affiliations
  • Mayo Clinic (US)
  • Emory University (US)
ORCID
Venue
Arthritis & Rheumatism
Publisher
Wiley
Published
2005-12
Volume
52
Issue
12
Pages
3839-3849
ISSN
  • 0004-3591 (ISSN-L)
  • 1529-0131
DOI
10.1002/art.21482
OpenAlex
W2046766565
Cited by
56
References
47
Citations by year
2024: 1 · 2023: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 7 · 2014: 4 · 2013: 3 · 2012: 3
FWCI
3.25
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1 d)
Locations
  • Arthritis & Rheumatism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Mayo Clinic
  • National Institute of Allergy and Infectious Diseases (R01AI044142, R01 AI57266, R01AI44142, R01-AI-41974)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527, R01AR42527)
Topics
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords
rheumatoid arthritis, effector memory T cells, CD4+CD28- T cells, tissue trafficking, chemokine receptors, CCR7, CCR5, CXCR4, RANTES, CXCL12, synovium, lymph nodes, T cell homing, IL-12, T cell survival, autoreactivity, T cell clonal expansion
MeSH terms
Animals, Arthritis, Rheumatoid, Cell Movement, Chimera, Humans, Immunologic Memory, CD4-Positive T-Lymphocytes, CD4 Antigens, Mice, SCID, Mice, Inbred NOD, CD28 Antigens, Interleukin-12, Adoptive Transfer, Receptors, Chemokine, Receptors, CCR5, Receptors, CXCR4, Mice, Receptors, CCR7

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