T-cell receptor genes in sarcoidosis.
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 V beta genes. Recent studies show that subgroups of patients with sarcoidosis are characterized by biased expression of specific V beta, V alpha, or gamma delta + 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 alpha beta + or gamma delta + 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.
Moller
D R
DR
Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. dmoller@welchlink.welch.jhu.edu
D019672:Genes, T-Cell Receptor; D006801:Humans; D008168:Lung / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000235:genetics* / Q000378:metabolism
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta