Chemokines: coded messages for T-cell missions

Viola, Antonella; Molon, Barbara; Contento, Rita Lucia

doi:10.2741/3158

Cited by 27 publications

(15 citation statements)

References 84 publications

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“…Activated or injured renal endothelium may upregulate these molecules, creating a pronounced gradient for DC, macrophage, and T cell recruitment and trafficking to secondary lymphoid tissues. Mature DCs subsequently activate lymphocytes to undergo clonal expansion and gain effector function (37), and a subset of effectors upregulate CXCR3 and migrate to inflamed tissues (38). Taken together, our results profile the changing pro-inflammatory microenvironment within a renal allograft that begins at reperfusion and results in the recruitment of a progressively activated T cell compartment in stable and rejecting allografts.…”

Section: Discussionmentioning

confidence: 99%

Chemokines and Their Receptors in Human Renal Allotransplantation

Weaver

Kleiner

et al. 2011

Transplantation

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Background Chemokines and their receptors play a critical role in leukocyte trafficking, and inhibition of select chemokines has been shown to attenuate kidney disease and allograft rejection in animal models. We therefore evaluated chemokine and chemokine receptor transcripts in human renal allograft biopsies, correlating transcript levels with clinical course and immunohistochemical analysis to relate chemokine expression to relevant clinical human disease phenotypes. Methods Renal biopsies were grouped as post-reperfusion (n=10), stable function (n=10), subclinical (n=10) or acute rejection (n=17), or calcineurin inhibitor nephrotoxicity (n=9) based on clinical presentation and histopathological assessment. Using quantitative real-time polymerase chain reaction analysis, chemokine transcripts were assessed relative to transcript levels in pre-procurement biopsies from live donor kidneys (n=15). Results Transcripts from several inflammatory chemokines (CCL3, CCL5, CXCL9, CXCL10 and CXCL11) and chemokine receptors (CCR5, CCR7 and CXCR3) were significantly elevated in allografts with subclinical and clinical acute rejection, indicating a strong polarization toward a TH1 effector phenotype during rejection. These transcripts also distinguished acutely rejecting allografts from allografts with non-rejection causes of renal dysfunction. Biopsies from patients with stable function without histological evidence of rejection had increased chemokine transcript levels that were qualitatively similar but quantitatively reduced compared to rejecting allografts. Conclusions This comprehensive evaluation of chemokines and their receptors in human renal transplantation defines associations between chemokine expression and clinical phenotypes, may have diagnostic utility, and highlights relevant pathways for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Chemokines and Their Receptors in Human Renal Allotransplantation

Weaver

Kleiner

et al. 2011

Transplantation

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“…It is known that stimuli encountered during T cell priming sets up a transcriptional programme in CD4 + T cells tailoring their function to combat the initiating stimulus whilst imprinting a lineage-specific and tissue-tropic chemokine receptor expression profile that facilitates migration to defined inflammatory sites (17). Chemokine receptor usage by naïve, T H 1, T H 2, T H 17 and Treg cells is well documented (17, 18), whereas the migratory capacity of the functionally dynamic T H 9 subset remains unknown. Therefore, in the present study, we examined chemokine receptor usage by T H 9 cells and determined the homing receptors involved in their recruitment to sites of allergic and autoimmune inflammation.…”

Section: Introductionmentioning

confidence: 99%

Distinct Chemokine Receptor Axes Regulate Th9 Cell Trafficking to Allergic and Autoimmune Inflammatory Sites

Kara

Comerford

Bastow

et al. 2013

The Journal of Immunology

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Migration of TH cells to peripheral sites of inflammation is essential for execution of their effector function. The recently described TH9 subset characteristically produces IL-9 and has been implicated in both allergy and autoimmunity. Despite this, the migratory properties of TH9 cells remain enigmatic. In this study, we have examined chemokine receptor usage by TH9 cells and demonstrate, in models of allergy and autoimmunity, that these cells express functional CCR3, CCR6 and CXCR3, chemokine receptors commonly associated with other, functionally opposed, effector TH subsets. Most TH9 cells that express CCR3 also express CXCR3 and CCR6 and expression of these receptors appears to account for the recruitment of TH9 cells to disparate inflammatory sites. During allergic inflammation, TH9 cells utilize CCR3 and CCR6 but not CXCR3 to home to the peritoneal cavity, whereas TH9 homing to the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) involves CXCR3 and CCR6 but not CCR3. These data provide the first insights into regulation of TH9 cell trafficking in allergy and autoimmunity.

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“…T cell extravasation from circulation and infiltration to tissue is a multi-step process that is mediated, in part, by lymphocyte-expressed chemokine receptors (CCRs) which recognize chemokines displayed on the luminal surface of vascular endothelium(1,2). The CXC chemokine receptor 3 (CXCR3) is expressed by Th1-skewed CD4 helper T cells(3,4) and Tc1-type CD8 effector T cells(5).…”

Section: Introductionmentioning

confidence: 99%

Peptide Vaccination in Montanide Adjuvant Induces and GM-CSF Increases CXCR3 and Cutaneous Lymphocyte Antigen Expression by Tumor Antigen–Specific CD8 T Cells

Clancy‐Thompson

King

Nunnley

et al. 2013

Cancer Immunology Research

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T cell infiltration of melanoma is associated with enhanced clinical efficacy and is a desirable endpoint of immunotherapeutic vaccination. Infiltration is regulated, in part, by chemokine receptors and selectin ligands on the surface of tumor-specific lymphocytes. Therefore, we investigated the expression of two homing molecules – CXCR3 and CLA – on vaccine-induced CD8 T cells, in the context of a clinical trial of a melanoma-specific peptide vaccine. Both CXCR3 and CLA have been associated with T cell infiltration of melanoma. We demonstrate that a single subcutaneous/intradermal administration of peptide vaccine in Montanide adjuvant induces tumor-specific CD8 T cells that are predominantly positive for CXCR3, with a subpopulation of CXCR3+CLA+ cells. Addition of GM-CSF significantly enhances CXCR3 expression and increases the proportion of CLA-expressing cells. Concurrent with CXCR3 and CLA expression, vaccine-induced CD8 cells express high levels of Tbet, IFN-γ, and IL-12Rβ1. Collectively, these studies demonstrate that peptide vaccination in adjuvant induces CD8 T cells with a phenotype that may support infiltration of melanoma.

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Chemokines: coded messages for T-cell missions

Cited by 27 publications

References 84 publications

Chemokines and Their Receptors in Human Renal Allotransplantation

Chemokines and Their Receptors in Human Renal Allotransplantation

Distinct Chemokine Receptor Axes Regulate Th9 Cell Trafficking to Allergic and Autoimmune Inflammatory Sites

Peptide Vaccination in Montanide Adjuvant Induces and GM-CSF Increases CXCR3 and Cutaneous Lymphocyte Antigen Expression by Tumor Antigen–Specific CD8 T Cells

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