The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.
Open accessAbstract
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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CCR5 has been used to identify Th1 cells, but it is expressed only on the more differentiated Th1 effector memory population.
“CCR5, another chemokine receptor with similar homing properties, has been also used to identify these cells [144, 145], but it is expressed only on the more differentiated Th1 effector memory population [146].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [145]
The Results (p. 3) place CCR5-positive blood T cells within a narrower, previously activated subset, and the Introduction (p. 1) describes CCR5 on activated and memory T cells. The cited paper does not establish that CCR5 is expressed only on the more differentiated Th1 effector-memory population. (LLM, conf=0.84)
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- 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)
- Venue
- Journal of Clinical Investigation
- Published
- 1998-02-15
- Volume
- 101
- Issue
- 4
- Pages
- 746-754
- ISSN
- 0021-9738 (ISSN-L)
- 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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