T-cell receptor genes in sarcoidosis

Research output: Contribution to journalReview articlepeer-review

Abstract

The pathogenesis of sarcoidosis involves activated, cytokine-producing T-cells and macrophages that regulate granulomatous inflammation. At sites of inflammation, T-cells demonstrate reduced surface density of the CD3 component of the T-cell receptor complex, a hallmark of T-cells activated through the T-cell antigen receptor pathway. The stimulus activating these T-cells is unknown. Conventional antigens selectively stimulate T-cells expressing T-cell receptors with specific variable (V) and hypervariable VDJ or VJ region amino acid sequences while superantigens stimulate larger subsets of T-cells based primarily on their expression of specific Vβ genes. Recent studies show that subgroups of patients with sarcoidosis are characterized by biased expression of specific Vβ, Vα, or γδ+ T-cell receptor genes in T-cell subsets from lung, blood and at sites of Kveim-Siltzbach skin reactions. In addition, investigations on the molecular structure of T-cell receptor genes in sarcoidosis provide direct evidence that biased expression of specific αβ+ or γδ+ T-cells at sites of inflammation involves selective expansion of oligoclonal populations of T-cells, consistent with an immune response to a conventional antigen(s). Together, these studies provide direct evidence that sarcoidosis is an antigen-driven disorder at sites of granulomatous inflammation. The identification of key, clonally-expanded T-cell populations in sarcoidosis provides a potential tool for determining the specific antigens involved in the pathogenesis of sarcoidosis.

Original languageEnglish (US)
Pages (from-to)158-164
Number of pages7
JournalSarcoidosis Vasculitis and Diffuse Lung Disease
Volume15
Issue number2
StatePublished - Sep 1998

Keywords

  • MHC molecules
  • Sarcoidosis
  • T-cell receptor
  • T-cell repertoire
  • γδ+ T-cells

ASJC Scopus subject areas

  • Internal Medicine
  • Immunology and Allergy
  • Pulmonary and Respiratory Medicine

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