Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)

Arthritis Res Ther. 2012 Apr 10;14(2):R73. doi: 10.1186/ar3794.

Abstract

Introduction: Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polarization.

Methods: Multicolor flow cytometry was used to analyze CCR4, CCR6, and intracellular cytokine expression of T cells from whole blood of GPA-patients (n = 26) and healthy controls (n = 20). CCR7 and CD45RA were included for phenotypic characterization.

Results: We found a significant increase in the percentages of circulating CCR4+ and CCR6+ cells within the total CD4+ T cell population in GPA. In contrast, there was no difference in the percentages of CD8+CCR4+ and CD8+CCR6+ T cells between GPA and healthy controls. CCR4 and CCR6 expression was largely confined to central (TCM) and effector memory T cells (TEM, TEMRA). A significant increase in the frequency of CCR4+ and CCR6+ TEMRA and CCR6+ TCM was shown in GPA. Of note, we could dissect CCR4 and CCR6 expressing CCR7+CD45RAmed very early memory T cells (TVEM) from genuine CCR7+CD45RAhigh naïve T cells lacking CCR4 and CCR6 expression for peripheral tissue-migration within the CCR7+CD45RA+ compartment. The frequencies of CCR4+ and CCR6+ TVEM were also significantly increased in GPA. An increased percentage of IL-17+ and IL-22+ cells was detected in the CCR6+ cell subsets and IL-4+ cells in the CRR4+ cell subset when compared with CD4+ cells lacking CCR4 and CCR6 expression.

Conclusions: Increased frequencies of circulating CCR4+ and CCR6+ memory T cell subsets including hitherto unreported TVEM suggest persistent T cell activation with the accumulation of CCR4+ and CCR6+ cells in GPA. CCR4 and CCR6 could be involved in the recruitment of T cells including cytokine-producing subsets to inflamed sites in GPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Granulomatosis with Polyangiitis / epidemiology
  • Granulomatosis with Polyangiitis / immunology
  • Granulomatosis with Polyangiitis / metabolism*
  • Humans
  • Immunologic Memory / physiology*
  • Leukocyte Common Antigens / biosynthesis*
  • Leukocyte Common Antigens / immunology
  • Male
  • Microscopic Polyangiitis / epidemiology
  • Microscopic Polyangiitis / immunology
  • Microscopic Polyangiitis / metabolism*
  • Middle Aged
  • Receptors, CCR4 / biosynthesis*
  • Receptors, CCR4 / immunology
  • Receptors, CCR6 / biosynthesis*
  • Receptors, CCR6 / immunology
  • Receptors, CCR7 / biosynthesis*
  • Receptors, CCR7 / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Young Adult

Substances

  • CCR4 protein, human
  • CCR6 protein, human
  • CCR7 protein, human
  • Receptors, CCR4
  • Receptors, CCR6
  • Receptors, CCR7
  • Leukocyte Common Antigens