Cytokine flexibility of early and differentiated memory T helper cells in juvenile idiopathic arthritis

J Rheumatol. 2004 Oct;31(10):2048-54.

Abstract

Objective: It has been suggested that CD45RO+CD27+ T cells represent recently activated memory cells, whereas CD45RO+CD27- T cells are activated memory T cells in the process of differentiating into effector cells. We investigated (1) CCR7 and CCR5 expression and (2) modulation of cytokine expression in "early" (CD27+) and "differentiated" (CD27-) memory CD4+ T cells from peripheral blood and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).

Methods: SF CD4+CD45RO+CD27+ and CD27- memory T cells from 6 patients with JIA were tested by flow cytometry for intracellular interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) after in vitro priming with CD3 and CD28 mAb in the presence of IL-4, and subsequent culture with IL-2.

Results: SF CD4+CD45RO+CD27+ cells contained higher proportions of CCR7+ (median 46% vs 23%) and lower proportions of CCR5+ (73% vs 90%) cells than paired CD27- T cells. Both CD27+ and CD27- memory T helper cells from SF displayed a higher IFN-gamma/IL-4 ratio than their peripheral blood counterparts. No significant difference was observed in the percentage of IFN-gamma-expressing cells between CD27+ (32%, range 4-47%) and CD27- (29.4%, range 5-52%) memory T helper cells from SF.

Conclusion: Irrespective of their differentiation stage, both CD27+ and CD27- SF memory T helper cells were found to switch from a proinflammatory to an antiinflammatory pattern of cytokine production.

MeSH terms

  • Arthritis, Juvenile / immunology*
  • Cell Differentiation
  • Child
  • Child, Preschool
  • Cytokines / immunology*
  • Female
  • Humans
  • Immunologic Memory*
  • Infant
  • Leukocyte Common Antigens / immunology
  • Lymphocyte Activation
  • Male
  • Receptors, CCR5 / immunology*
  • Receptors, CCR7
  • Receptors, Chemokine / immunology*
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology*

Substances

  • CCR7 protein, human
  • Cytokines
  • Receptors, CCR5
  • Receptors, CCR7
  • Receptors, Chemokine
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Leukocyte Common Antigens