Pulmonary Sarcoidosis

Kirtland, Steven H.; Winterbauer, Richard

doi:10.1055/s-2007-1006334

Cited by 7 publications

(1 citation statement)

References 40 publications

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“…As the sarcoidosis subjects demonstrated a range of pulmonary function abnormalities and chest radiographic disease, we also compared total iNKT‐cell frequencies and absolute counts between subjects in each of the defined disease stages (Stages I–IV, as described in the Materials and methods ). Stage IV disease is defined by evidence of lung fibrosis and is considered to be irreversible compared with Stage I disease, which has been reported to resolve spontaneously in up to 70% of subjects . Stage IV subjects had significantly lower iNKT‐cell frequencies compared with both controls and subjects with Stage I disease (Fig.…”

Section: Resultsmentioning

confidence: 99%

Invariant natural killer T (iNKT) cell exhaustion in sarcoidosis

et al. 2013

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Summary Invariant natural killer T (iNKT) cells are integral components of immune responses during many chronic diseases, yet their surface phenotypes, subset distribution, and polyfunctional capacity in this environment are largely unknown. Therefore, using flow cytometry, we determined iNKT phenotypic and functional characteristics in subjects with the chronic inflammatory disease sarcoidosis and matched controls. We found that sarcoidosis subjects displayed lower iNKT frequencies, which correlated with lung fibrosis, C-reactive protein levels, and other measures of clinical disease. The CD4− CD8− (DN) iNKT cell population was selectively lower in diseased individuals and the remaining DN iNKT cells exhibited higher frequencies of the activation markers CD69 and CD56. Functionally, both total IFN-gamma+ and the dual-functional IFN-gamma+ TNF-alpha+ iNKT cells were decreased in sarcoidosis subjects and these functional defects correlated with total iNKT circulating frequencies. As the loss of polyfunctionality can reflect functional exhaustion, we measured the surface antigens PD-1 and CD57 and found that levels inversely correlated with dual-functional iNKT cell percentages. These findings reveal that, similar to traditional T cells, iNKT cells may also undergo functional exhaustion, and that circulating iNKT frequencies reflect these defects. PD-1 antagonists may therefore be attractive therapeutic candidates for sarcoidosis and other iNKT-mediated chronic diseases.

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Section: Resultsmentioning

confidence: 99%