Pathways of T cell activation and terminal differentiation in chronic inflammation

Curr Drug Targets Inflamm Allergy. 2005 Jun;4(3):287-93. doi: 10.2174/1568010054022042.

Abstract

Immune and inflammatory responses are governed by antigen-specific T cells, whose activation, differentiation and effector function are induced by signals delivered via the T cell antigen receptor (TCR) and by costimulatory and cytokine receptors. The molecular events leading to the activation of naïve T cells have been extensively studied and are well characterized. Much less is known about the molecular and biochemical events regulating the activation of T cells in chronic inflammatory diseases such as rheumatoid arthritis (RA). This review examines the current state of knowledge of T cell activation in chronic inflammation, focusing on RA, and summarizes experimental data which indicate that the chronic inflammatory process may profoundly affect TCR and cytokine signal transduction pathways. We present evidence suggesting that in chronic inflammation, the antigen-driven TCR-mediated processes are attenuated, while cytokine-driven effector responses are sustained or even enhanced. The possible implications of this inbalance are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / physiopathology
  • Cell Differentiation / physiology
  • Chronic Disease
  • Cytokines / physiology
  • Humans
  • Inflammation / pathology
  • Inflammation / physiopathology*
  • Lymphocyte Activation / physiology*
  • Phenotype
  • Signal Transduction / physiology
  • T-Lymphocytes / physiology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Cytokines
  • Tumor Necrosis Factor-alpha