Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity

S. Sebastiani, P. Allavena, C. Albanesi, F. Nasorri, G. Bianchi, C. Traidl, S. Sozzani, G. Girolomoni, A. Cavani

Research output: Contribution to journalArticlepeer-review

Abstract

We have investigated the chemokine receptor expression and migratory behavior of a new subset of nickel-specific skin-homing regulatory CD4+ T cells (ThIL-10) releasing high levels of IL-10, low IFN-γ, and undetectable IL-4. These cells inhibit in a IL-10-dependent manner the capacity of dendritic cells to activate nickel-specific Tc1 and Th1 lymphocytes. RNase protection assay and FACS analysis revealed the expression of a vast repertoire of chemokine receptors on resting ThIL-10, including the Th1-associated CXCR3 and CCRS, and the Th2-associated CCR3, CCR4, and CCR8, the latter at higher levels compared with Th2 cells. The most active chemokines for resting ThIL-10, in terms of calcium mobilization and in vitro migration, were in order of potency: CCL2 (monocyte chemoattractant protein-1, CCR2 ligand), CCL4 (macrophage-inflammatory protein-1β, CCR5 ligand), CCL3 (macrophage-inflammatory protein-1α, CCR1/5 ligand), CCL17 (thymus and activation-regulated chemokine, CCR4 ligand), CCL1 (I-309, CCR8 ligand), CXCL12 (stromal-derived factor-1, CXCR4), and CCL11 (eotaxin, CCR3 ligand). Consistent with receptor expression down-regulation, activated ThIL-10 exhibited a reduced or absent response to most chemokines, but retained a significant migratory capacity to I-309, monocyte chemoattractant protein-1, and thymus and activation-regulated chemokine. I-309, which was ineffective on Th1 lymphocytes, attracted more efficiently ThIL-10 than Th2 cells. I-309 and CCR8 mRNAs were not detected in unaffected skin and were up-regulated at the skin site of nickel-allergic reaction, with an earlier expression kinetics compared with IL-10 and IL-4. Results indicate that skin-homing regulatory ThIL-10 lymphocytes coexpress functional Th1- and Th2-associated chemokine receptors, and that CCR8/I-309-driven recruitment of both resting and activated ThIL-10 cells may be critically involved in the regulation of Th1-mediated skin allergic disorders.

Original languageEnglish
Pages (from-to)996-1002
Number of pages7
JournalJournal of Immunology
Volume166
Issue number2
Publication statusPublished - Jan 15 2001

ASJC Scopus subject areas

  • Immunology

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