Cited by 1,359Chemokine receptors and signalingCell Adhesion Molecules ResearchMacrophage Migration Inhibitory Factor

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The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.

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Qin, S, Rottman, J B, Myers, P, Kassam, N, Weinblatt, M, Loetscher, M, Koch, A E, Moser, B, Mackay, C R·1998·Journal of Clinical Investigation

DOI 10.1172/jci1422PMC PMC508621

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Abstract

T cells infiltrating inflammatory sites are usually of the activated/memory type. The precise mechanism for the positioning of these cells within tissues is unclear. Adhesion molecules certainly play a role; however, the intricate control of cell migration appears to be mediated by numerous chemokines and their receptors. Particularly important chemokines for activated/memory T cells are the CXCR3 ligands IP-10 and Mig and the CCR5 ligands RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta. We raised anti-CXCR3 mAbs and were able to detect high levels of CXCR3 expression on activated T cells. Surprisingly, a proportion of circulating blood T cells, B cells, and natural killer cells also expressed CXCR3. CCR5 showed a similar expression pattern as CXCR3, but was expressed on fewer circulating T cells. Blood T cells expressing CXCR3 (and CCR5) were mostly CD45RO+, and generally expressed high levels of beta1 integrins. This phenotype resembled that of T cells infiltrating inflammatory lesions. Immunostaining of T cells in rheumatoid arthritis synovial fluid confirmed that virtually all such T cells expressed CXCR3 and approximately 80% expressed CCR5, representing high enrichment over levels of CXCR3+ and CCR5+ T cells in blood, 35 and 15%, respectively. Analysis by immunohistochemistry of various inflamed tissues gave comparable findings in that virtually all T cells within the lesions expressed CXCR3, particularly in perivascular regions, whereas far fewer T cells within normal lymph nodes expressed CXCR3 or CCR5. These results demonstrate that the chemokine receptor CXCR3 and CCR5 are markers for T cells associated with certain inflammatory reactions, particularly TH-1 type reactions. Moreover, CXCR3 and CCR5 appear to identify subsets of T cells in blood with a predilection for homing to these sites.

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Self-citation

Authors: Qin, S., Rottman, J. B., Myers, P., Kassam, N., Weinblatt, M., Loetscher, M., Koch, A. E., Moser, B., & Mackay, C. R.
Affiliations: Brigham and Women's Hospital (US)
University of Bern (CH)
Northwestern University (US)
ORCID: Rottman, J B
Weinblatt, M
Moser, B
Mackay, C R
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1998-02-15
Volume: 101
Issue: 4
Pages: 746-754
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci1422
PMC: PMC508621
OpenAlex: W2081596482
Cited by: 1,359
References: 39
Citations by year: 2026: 6 · 2025: 25 · 2024: 11 · 2023: 20 · 2022: 24 · 2021: 33 · 2020: 23 · 2019: 33 · 2018: 32 · 2017: 33 · 2016: 24 · 2015: 46 · 2014: 52 · 2013: 38 · 2012: 45
FWCI: 37.11
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
Keywords: CXCR3, CCR5, chemokine receptors, T cell subsets, T cell homing, inflammatory cell infiltration, Th1 response, CXCL10, RANTES, CCL22, CCL19, CD45RO, beta1 integrin, T cell migration, lymph node T cells
MeSH terms: Animals, Antibodies, Monoclonal, Chemotaxis, Humans, Immunologic Memory, Inflammation, Leukocytes, Lymphocyte Activation, Lymphocytes, Mice, Inbred BALB C, Synovial Fluid, Tumor Cells, Cultured, Biomarkers, T-Lymphocyte Subsets, Chemokines, Receptors, Chemokine, Receptors, CCR5, Chemokines, CXC, Mice, Chemokine CXCL10, Receptors, CXCR3

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The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.

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