Involvement of T cells and alterations in T cell receptors in sarcoidosis.

Sarcoidosis is recognized to be a multisystem granulomatous disease characterized by activated, cytokine-producing T cells and macrophages at sites of inflammation. The purpose of this article is to review new evidence concerning the role of T cells in sarcoidosis. Recent work on the molecular structure and repertoire of T cell receptor genes in sarcoidosis provide direct evidence that sarcoidosis is characterized by selective expansions of oligoclonal populations of T cells at sites of inflammation, consistent with local antigen-driven immune responses. In addition, data on cytokine production in sarcoidosis indicate that tissue inflammation is dominated by expression of type 1 (T helper 1) cytokines such as interferon-gamma and interleukin-12 that, in keeping with experimental models of granulomatous diseases, likely orchestrate the granulomatous response. These studies offer new insight into the molecular mechanisms of granuloma formation in sarcoidosis and provide a framework for developing new therapeutic strategies for the treatment of this disease.