Heterogeneity of CD4 and CD8+ memory T cells in localized and generalized Wegener's granulomatosis

Arthritis Res Ther. 2003;5(1):R25-31. doi: 10.1186/ar610. Epub 2002 Oct 24.

Abstract

Memory T cells display phenotypic heterogeneity. Surface antigens previously regarded as exclusive markers of naive T cells, such as L-selectin (CD62L), can also be detected on some memory T cells. Moreover, a fraction of CD45RO+ (positive for the short human isoform of CD45) memory T cells reverts to the CD45RA+ (positive for the long human isoform of CD45) phenotype. We analyzed patients with biopsy-proven localized Wegener's granulomatosis (WG) (n = 5), generalized WG (n = 16) and age- and sex-matched healthy controls (n = 13) to further characterize memory T cells in WG. The cell-surface expression of CD45RO, CD45RA, CD62L, CCR3, CCR5 and CXCR3 was determined on blood-derived T cells by four-color flow cytometric analysis. The fractions of CCR5+ and CCR3+ cells within the CD4+CD45RO+ and CD8+CD45RO+ memory T cell populations were significantly expanded in localized and generalized WG. The mean percentage of Th1-type CCR5 expression was higher in localized WG. Upregulated CCR5 and CCR3 expression could also be detected on a fraction of CD45RA+ T cells. CD62L expression was seen on approximately half of the memory T cell populations expressing chemokine receptors. This study demonstrates for the first time that expression of the inducible inflammatory chemokine receptors CCR5 and CCR3 on CD45RO+ memory T cells, as well as on CD45RA+ T cells ('revertants'), contributes to phenotypic heterogeneity in an autoimmune disease, namely WG. Upregulated CCR5 and CCR3 expression suggests that the cells belong to the effector memory T cell population. CCR5 and CCR3 expression on CD4+ and CD8+ memory T cells indicates a potential to respond to chemotactic gradients and might be important in T cell migration contributing to granuloma formation and vasculitis in WG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Granulomatosis with Polyangiitis / immunology*
  • Humans
  • Immunologic Memory*
  • L-Selectin / metabolism
  • Leukocyte Common Antigens / analysis
  • Receptors, CCR3
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR3
  • Receptors, Chemokine / metabolism
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology*

Substances

  • CCR3 protein, human
  • CXCR3 protein, human
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CXCR3
  • Receptors, Chemokine
  • L-Selectin
  • Leukocyte Common Antigens