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State of the Art. Role of CD4⁺ T Cells in Sarcoidosis

¹ Division of Respiratory Medicine, Department of Medicine, Karolinska University Hospital Solna, Stockholm, Sweden

Correspondence and requests for reprints should be addressed to Johan Grunewald, M.D., Ph.D., Department of Medicine, Division of Respiratory Medicine, Lung Research Laboratory L4:01, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden. E-mail: johan.grunewald{at}ki.se

ABSTRACT

Activated pulmonary CD4⁺ T lymphocytes of the Th-1 type are essential for the inflammatory process in sarcoidosis, and IFN- production is crucial for the characteristic granuloma formation. Both the T cells and their inflammatory mediators may constitute possible targets for immunotherapy. A particular T-cell subset, the T-cell receptor (TCR) AV2S3⁺ bronchoalveolar lavage (BAL) CD4⁺ T cells, is found at dramatically increased levels in the BAL fluid of human leukocyte antigen (HLA)-DRB1*0301–positive and/or HLA-DRB3*0101–positive patients with sarcoidosis. The AV2S3⁺ BAL CD4⁺ T cells strongly associate with the sarcoid inflammation, and future studies on this particular T-cell subset to reveal their specificity may lead to the identification of sarcoidosis-specific antigen(s). T-cell subpopulations with regulatory functions (i.e., natural killer T cells and T regulatory cells) have recently been described as abnormal in sarcoidosis. Dysfunctional regulatory T cells may allow T effector cells to contribute to the formation of granulomas, and they may thus be relevant for the inflammatory process in this disease. These findings are exciting news and will be of help in designing new treatment strategies.

Key Words: T cells • sarcoidosis • granuloma

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