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Sarcoidosis Th17 Cells are ESAT-6 Antigen Specific but Demonstrate Reduced IFN-γ Expression

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Abstract

Rationale

Sarcoidosis is a granulomatous disease of unknown etiology. Many patients with sarcoidosis demonstrate antigen-specific immunity to mycobacterial virulence factors. Th-17 cells are crucial to the immune response in granulomatous inflammation, and have recently been shown to be present in greater numbers in the peripheral blood and bronchoalveolar lavage (BAL) fluid (BALF) of sarcoidosis patients than healthy controls. It is unclear whether Th-17 cells in sarcoidosis are specific for mycobacterial antigens, or whether they have similar functionality to control Th-17 cells.

Methods

Flow cytometry was used to determine the numbers of Th-17 cells present in the peripheral blood and BALF of patients with sarcoidosis, the percentage of Th-17 cells that were specific to the mycobacterial virulence factor ESAT-6, and as well as to assess IFN-γ expression in Th-17 cells following polyclonal stimulation.

Results

Patients with sarcoidosis had greater numbers of Th-17 cells in the peripheral blood and BALF than controls and produced significantly more extracellular IL-17A (p = 0.03 and p = 0.02, respectively). ESAT-6 specific Th-17 cells were present in both peripheral blood and BALF of sarcoidosis patients (p < 0.001 and p = 0.03, respectively). After polyclonal stimulation, Th-17 cells from sarcoidosis patients produced less IFN-γ than healthy controls.

Conclusions

Patients with sarcoidosis have mycobacterial antigen-specific Th-17 cells peripherally and in sites of active sarcoidosis involvement. Despite the Th1 immunophenotype of sarcoidosis immunology, the Th-17 cells have reduced IFN-γ expression, compared to healthy controls. This reduction in immunity may contribute to sarcoidosis pathogenesis.

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Acknowledgments

We thank the sarcoidosis patients who participated in this study. We also thank the following agencies for supporting this research: National Institutes of Health K01HL103179-01 and Foundation for Sarcoidosis Research grant to K.R., T32HL069765-08 to B.R., T35 HL090555 to K.P., T32HL094296 to T.T., and RO1-HL83839, MO1 RR-00095, The Eliassen Foundation, The Pierce Foundation, 1 U01 HL112694-01 and Vanderbilt CTSA grant 1 UL1 RR024975 to W.P.D.

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Authors and Affiliations

  1. Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical School, 21st Avenue South, Medical Center North, Suite T-1218 MCN, Nashville, TN, 37232-2363, USA

    Bradley W. Richmond

  2. Division of Infectious Diseases, Vanderbilt University Medical School, Nashville, TN, 37232-2363, USA

    Kristen Ploetze, Joan Isom, Isfahan Chambers-Harris, Nicole A. Braun, Thyneice Taylor & Wonder P. Drake

  3. Respiratory Institute, Cleveland Clinic, Cleveland, OH, 44195, USA

    Susamma Abraham & Dan A. Culver

  4. University of Vermont College of Medicine, Nashville, TN, 37232-2363, USA

    Yolanda Mageto

  5. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, 37232-2363, USA

    Kyra A. Oswald-Richter & Wonder P. Drake

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  1. Bradley W. Richmond
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  2. Kristen Ploetze
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Correspondence to Bradley W. Richmond.

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Bradley W. Richmond and Kristen Ploetze are co first authors.

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Richmond, B.W., Ploetze, K., Isom, J. et al. Sarcoidosis Th17 Cells are ESAT-6 Antigen Specific but Demonstrate Reduced IFN-γ Expression. J Clin Immunol 33, 446–455 (2013). https://doi.org/10.1007/s10875-012-9817-6

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  • DOI: https://doi.org/10.1007/s10875-012-9817-6

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