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- Title
Invariant natural killer T (i NKT) cell exhaustion in sarcoidosis.
- Authors
Snyder‐Cappione, Jennifer E.; Nixon, Douglas F.; Chi, Joyce C.; Nguyen, Michelle‐Linh T.; Kirby, Christopher K.; Milush, Jeffrey M.; Koth, Laura L.
- Abstract
Invariant natural killer T (i NKT) 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 i NKT cell phenotypic and functional characteristics in subjects with chronic inflammatory disease sarcoidosis and matched controls. We found that sarcoidosis subjects displayed lower i NKT-cell frequencies, which correlated with lung fibrosis, C-reactive protein levels, and other measures of clinical disease. The CD4− CD8− (double negative, DN) i NKT-cell population was selectively lower in diseased individuals and the remaining DN i NKT cells exhibited higher frequencies of the activation markers CD69 and CD56. Functionally, both total IFN-γ+ and the dual-functional IFN-γ+ TNF-α+ i NKT cells were decreased in sarcoidosis subjects and these functional defects correlated with total i NKT-cell circulating frequencies. As the loss of polyfunctionality can reflect functional exhaustion, we measured the surface antigens programmed death-1 receptor and CD57 and found that levels inversely correlated with dual-functional i NKT-cell percentages. These findings reveal that, similar to traditional T cells, i NKT cells may also undergo functional exhaustion, and that circulating i NKT-cell frequencies reflect these defects. Programmed death-1 receptor antagonists may therefore be attractive therapeutic candidates for sarcoidosis and other i NKT-cell-mediated chronic diseases.
- Publication
European Journal of Immunology, 2013, Vol 43, Issue 8, p2194
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201243185