Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Though patients develop inflammation at active sites of involvement, an anergic phenotype dominates peripherally. Recent reports suggest that dysfunction in the CD4+ T cell compartment contributes to the anergic responses, yet little is known about the role of CD8+ T cells. Chronic inflammation studies demonstrate that persistent antigen stimulation leads to CD8+ T cell exhaustion. Furthermore, an increase in CD8+ exhausted T cells has been shown to correlate with disease severity in multiple chronic inflammatory diseases. Therefore we hypothesized that CD8+ T cell exhaustion contributes to sarcoidosis disease severity. We report that expression of inhibitory receptors including PD-1 are upregulated on CD8+ T cells in sarcoidosis subjects with active disease, whereas cytokine production, proliferation, and cytotoxicity are impaired. In addition, we assessed CD8+ T cell function during active disease and upon disease improvement. Improvement of disease correlated with reversal of the exhausted phenotype. These results demonstrate that CD8+ T cell exhaustion contributes to immune dysregulation in sarcoidosis. Importantly, restoration of CD8+ T cell function results in disease resolution indicating that CD8+ T cell exhaustion may correlate with disease severity and thus, exhausted CD8+ T cells may be a potential biomarker to predict disease outcome.
- Copyright © 2013 by The American Association of Immunologists, Inc.