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

S Sebastiani1, P Allavena, C Albanesi

  • 1Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.

Journal of Immunology (Baltimore, Md. : 1950)
|January 6, 2001
PubMed

Insights

New regulatory T cells (Th(IL-10)) that home to the skin were identified. These cells express both Th1 and Th2 chemokine receptors, suggesting a role in regulating skin allergic reactions.

Area of Science:

  • Immunology
  • Dermatology
  • Allergy Research

Background:

  • Regulatory T cells (Tregs) play a crucial role in immune homeostasis and preventing autoimmune diseases.
  • CD4(+) T cells are key players in adaptive immunity, with subsets like Th1 and Th2 cells mediating distinct immune responses.
  • Chemokine receptors are essential for guiding immune cell migration to specific tissues.

Purpose of the Study:

  • To investigate the chemokine receptor expression and migratory behavior of a novel subset of nickel-specific, skin-homing regulatory CD4(+) T cells (Th(IL-10)).
  • To determine the role of these Th(IL-10) cells in modulating immune responses, particularly in the context of skin allergies.
  • To elucidate the specific chemokines and receptors involved in the recruitment of Th(IL-10) cells to inflamed skin.

Main Methods:

  • Flow cytometry (FACS) and RNase protection assays were used to analyze chemokine receptor expression on Th(IL-10) cells.
  • In vitro migration assays and calcium mobilization studies were performed to assess the migratory responses of Th(IL-10) cells to various chemokines.
  • Quantitative analysis of chemokine and cytokine mRNA expression in skin samples from nickel-allergic reactions.

Main Results:

  • A new subset of nickel-specific regulatory CD4(+) T cells (Th(IL-10)) was identified, characterized by high IL-10 production and skin-homing potential.
  • These Th(IL-10) cells express a broad range of chemokine receptors, including Th1-associated (CXCR3, CCR5) and Th2-associated (CCR3, CCR4, CCR8) receptors.
  • The CCR8 ligand, I-309, demonstrated potent chemoattractant activity for Th(IL-10) cells, with CCR8 and I-309 expression upregulated at nickel-induced skin allergic sites.

Conclusions:

  • Skin-homing regulatory Th(IL-10) lymphocytes coexpress functional Th1- and Th2-associated chemokine receptors.
  • The CCR8/I-309 axis is likely critical for the recruitment of Th(IL-10) cells to skin allergic inflammation sites.
  • These findings suggest a significant role for Th(IL-10) cells in the regulation of Th1-mediated skin allergic disorders.

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