Article: The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.
The Journal of clinical investigation
1998 Volume 101, Issue 4, Page(s) 746–754
Abstract: T cells infiltrating inflammatory sites are usually of the activated/memory type. The precise ... and their receptors. Particularly important chemokines for activated/memory T cells are the CXCR3 ... on activated T cells. Surprisingly, a proportion of circulating blood T cells, B cells, and ...
| 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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| MeSH term(s) | Animals ; Antibodies, Monoclonal/immunology ; Biomarkers ; Chemokine CXCL10 ; Chemokines/immunology ; Chemokines, CXC ; Chemotaxis ; Humans ; Immunologic Memory/immunology ; Inflammation/immunology ; Leukocytes/immunology ; Lymphocyte Activation/immunology ; Lymphocytes/immunology ; Mice ; Mice, Inbred BALB C ; Receptors, CCR5/immunology ; Receptors, CXCR3 ; Receptors, Chemokine/biosynthesis ; Receptors, Chemokine/immunology ; Synovial Fluid/cytology ; Synovial Fluid/immunology ; T-Lymphocyte Subsets/cytology ; T-Lymphocyte Subsets/immunology ; Tumor Cells, Cultured |
| Chemical Substances | Antibodies, Monoclonal ; Biomarkers ; CXCR3 protein, human ; Chemokine CXCL10 ; Chemokines ; Chemokines, CXC ; Cxcr3 protein, mouse ; Receptors, CCR5 ; Receptors, CXCR3 ; Receptors, Chemokine |
| Language | English |
| Publishing date | 1998-02-15 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 3067-3 |
| ISSN | 1558-8238 ; 0021-9738 |
| ISSN (online) | 1558-8238 |
| ISSN | 0021-9738 |
| DOI | 10.1172/JCI1422 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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