Abnormal expression of intracellular cytokines and chemokine receptors in peripheral blood T lymphocytes from patients with systemic sclerosis

Clin Exp Immunol. 2002 Dec;130(3):548-56. doi: 10.1046/j.1365-2249.2002.02017.x.

Abstract

In patients with systemic sclerosis (SSc), there are conflicting findings regarding which is predominant between type 1 and type 2 immune responses. To determine the balance between type 1 and type 2 T lymphocytes in peripheral blood from SSc patients, we investigated the expression of intracellular cytokines, such as interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-13, and chemokine receptors such as CXCR3 and CCR4 by flow cytometry. The frequency of IFN-gamma-producing cells among CD8+ cells was significantly increased in patients with diffuse cutaneous SSc (n = 11, P < 0.0001) and limited cutaneous SSc (lSSc; n= 16, P < 0.0001) compared with normal controls (n = 17) while there was no significant difference in the frequency of IL-4- or IL-13-producing cells. In contrast, the frequency of IFN-gamma- or IL-4-producing cells among CD4+ cells was similar between the three groups. Similar results were obtained when absolute numbers were assessed. The frequency of IFN-gamma-producing cells among CD8+ cells inversely correlated with percentage DLco in SSc patients (r = - 0.650, P < 0.005). CXCR3+ CD8+ cells selectively produced IFN-gamma, and the frequency of CXCR3+ CD45RO+ cells among CD8+ cells was higher in lSSc patients (n = 14, P < 0.01) than in normal controls (n = 22). In contrast, there was no significant difference in the frequencies of CXCR3- or CCR4-expressing CD45RO+ cells among CD4+ cells. These results demonstrate the predominance of type 1 cytokine-producing cells (Tc1 cells) in peripheral blood CD8+ T cells from SSc patients, but no definite Th1/Th2 imbalance in CD4+ T cells. Tc1 cells may be associated with pulmonary vascular damage in SSc.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • Case-Control Studies
  • Cytokines / analysis*
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / blood
  • Interleukin-13 / analysis
  • Interleukin-2 / analysis
  • Interleukin-4 / analysis
  • Intracellular Fluid / immunology
  • Male
  • Middle Aged
  • Receptors, CCR4
  • Receptors, CXCR3
  • Receptors, Chemokine / analysis*
  • Scleroderma, Systemic / immunology*
  • Statistics, Nonparametric
  • T-Lymphocytes / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Biomarkers
  • CCR4 protein, human
  • CXCR3 protein, human
  • Cytokines
  • Interleukin-13
  • Interleukin-2
  • Receptors, CCR4
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Interleukin-4
  • Interferon-gamma