Unique Chemotactic Response Profile and Specific Expression of Chemokine Receptors Ccr4 and Ccr8 by Cd4+Cd25+ Regulatory T Cells
By A. Iellem, M. Mariani, R. Lang, H. Recalde, P. Panina-Bordignon, F. Sinigaglia, D. d'Ambrosio. Journal of Experimental Medicine, 2001
993 citations recorded by the source corpus.
Chemokines dictate regional trafficking of functionally distinct T cell subsets. In rodents and humans, a unique subset of CD4+CD25+ cytotoxic T lymphocyte antigen (CTLA)-4+ regulatory T cells (Treg) has been proposed to control peripheral tolerance. However, the molecular basis of immune suppression and the trafficking properties of Treg cells are still unknown. Here, we determined the chemotactic response profile and chemokine receptor expression of human blood-borne CD4+CD25+ Treg cells. These Treg cells were found to vigorously respond to several inflammatory and lymphoid chemokines. Treg cells specifically express the chemokine receptors CCR4 and CCR8 and represent a major subset of circulating CD4+ T cells responding to the chemokines macrophage-derived chemokine (MDC)/CCL22, thymus and activation-regulated chemokine (TARC)/CCL17, I-309/CCL1, and to the virokine vMIP-I (ligands of CCR4 and CCR8). Blood-borne CD4+ T cells that migrate in response to CCL1 and CCL22 exhibit a reduced alloproliferative response, dependent on the increased frequency of Treg cells in the migrated population. Importantly, mature dendritic cells preferentially attract Treg cells among circulating CD4+ T cells, by secretion of CCR4 ligands CCL17 and CCL22. Overall, these results suggest that CCR4 and/or CCR8 may guide Treg cells to sites of antigen presentation in secondary lymphoid tissues and inflamed areas to attenuate T cell activation.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/2f11feb5c09213f93855b14b84489df63fb792cc
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Citations in the corpus
- CD4+CD25+ suppressor T cells: more questions than answers (2002, neutral): “The studies of Iellem et al.(61) and Bystry et al.”
- Cytokines in atherosclerosis: pathogenic and regulatory pathways. (2006, background): “CCR4 and CCR8 seem to be specifically expressed by CD4 CD25 Treg cells (211, 300).”
- Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment (2014, background): “Intratumoral Treg trafficking is mediated through the CCL22/CCR4 axis [95].”
- Regulatory T Cells Selectively Express Toll-like Receptors and Are Activated by Lipopolysaccharide (2003, background): “Accordingly, evidence exists for rapid Treg migration to inflammatory sites, likely as a result of the constitutive expression of chemokine receptors (6) and high sensitivity to inflammatory chemokines (7).”
- NF-κB: linking inflammation and immunity to cancer development and progression (2005, background): “Furthermore, CC-chemokine ligand 22 (CCL22; also known as MDC), and to a lesser extent CCL17 (also known as TARC), can attract regulatory T (T Reg ) cell”
- International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors (2014, neutral): “…steady state include human and mouse monocytes and macrophages (Zaballos et al., 1996; Tiffany et al., 1997; Hoshino et al., 2007), thymocytes (Annunziato et al., 2002), and regulatory T cells (Iellem et al., 2001; Kremer et al., 2001; Soler et al., 2006; Ahern et al., 2009; Zheng et al., 2009).”
- Chemokines and chemokine receptors: positioning cells for host defense and immunity. (2014, result): “Before this understanding of the heterogeneity of the Treg population, investigators had found that the basal repertoire of chemokines in a nonsegregated human memory Treg population had an increased expression of CCR4 and CCR8 when compared with both naive and memory CD25−CD4+ T cells (251).”