T cell responses to mycobacterial catalase-peroxidase profile a pathogenic antigen in systemic sarcoidosis.
Sarcoidosis is a systemic granulomatous disease associated with local epithelioid granulomas, CD4(+) T cells, and Th1 cytokines. The tissue Ags that drive this granulomatous inflammation are uncertain. In this study, we used IFN-gamma-ELISPOT assays and flow cytometry to assess lung and blood T cell responses to the candidate pathogenic Ag, Mycobacterium tuberculosis catalase-peroxidase (mKatG) in patients with sarcoidosis from two centers. Despite differences in patient phenotypic, genetic, and prognostic characteristics, we report that T cell responses to mKatG were remarkably similar in these cohorts, with higher frequencies of mKatG-reactive, IFN-gamma-expressing T cells in the blood of sarcoidosis patients compared with nontuberculosis sensitized healthy controls, and (in a subset) in greater numbers than T cells reactive to purified protein derivative. In sarcoidosis, mKatG-reactive CD4(+) Th1 cells preferentially accumulated in the lung, indicating a compartmentalized response. Patients with or without Löfgren syndrome had similar frequencies of mKatG specific IFN-gamma-expressing blood T cells. Circulating mKatG-reactive T cells were found in chronic active sarcoidosis but not in patients with inactive disease. Together, these results demonstrate that T cell responses to mKatG in sarcoidosis fit a profile expected for a pathogenic Ag, supporting an immunotherapeutic approach to this disease.
Chen
Edward S
ES
Department of Medicine, Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Wahlström
Jan
J
Song
Zhimin
Z
Willett
Matthew H
MH
Wikén
Maria
M
Yung
Rex C
RC
West
Erin E
EE
McDyer
John F
JF
Zhang
Ying
Y
Eklund
Anders
A
Grunewald
Johan
J
Moller
David R
DR
D000328:Adult; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002374:Catalase / Q000097:blood / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000276:immunology* / Q000472:pathogenicity; D012507:Sarcoidosis / Q000276:immunology* / Q000382:microbiology* / Q000628:therapy; D013548:Sweden; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014373:Tuberculin / Q000276:immunology; D014481:United States
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D014373:Tuberculin; D007371:Interferon-gamma; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis