Hodgkin lymphoma is caused by a minority population of malignant Hodgkin and Reed-Sternberg (HRS) cells that recruit an abundance of inflammatory cells. The long-term survival of HRS cells among the vast majority of immune cells indicates that they have developed potent immune escape mechanisms. We report that the TNF receptor family member CD137 (TNFRSF9) is expressed on HRS cells, while normal B cells, from which HRS cells are most often derived, do not express CD137. In 48 of 53 cases of classical Hodgkin lymphoma, CD137 was detected on HRS cells. Ectopically expressed CD137 transferred by trogocytosis from HRS cells to neighboring HRS and antigen-presenting cells, which constitutively express the CD137 ligand (CD137L and TNFSF9), became associated with CD137L and the CD137-CD137L complex was internalized. Disappearance of CD137L from the surface of HRS and antigen-presenting cells led to reduced costimulation of T cells through CD137, reducing IFN-g release and proliferation. Our results reveal a new regulatory mechanism for CD137L expression that mediates immune escape by HRS cells, and they identify CD137 as a candidate target for immunotherapy of Hodgkin lymphoma. Cancer Res; 73(2); 652-61. Ó2012 AACR.
Background-Azithromycin is a macrolide antibiotic that is active against several periodontal pathogens. Macrolides are taken up and concentrated inside gingival fibroblasts, which could influence their pharmacokinetics. This study tested the hypothesis that steady-state levels of azithromycin are higher and more sustained in gingival crevicular fluid (GCF) than in serum.
The thermographer was effective in capturing temperature changes in the ocular surface. The temperature difference 3 s after blinking appears to be correlated with lower TMH and Schirmer test values.
Azithromycin enhances the response to root planing and produces anti-inflammatory effects in treating chronic lung disease. This led us to hypothesize that azithromycin inhibits inflammatory mediator production in gingiva, leading to decreased gingival crevicular fluid (GCF) volume. To test this hypothesis, ten periodontally healthy volunteers received azithromycin every 24 hours for 48 hours. GCF samples were collected from twelve maxillary interproximal sites prior to azithromycin (baseline) and 2, 4, 7 and 14 days later. Samples were assayed for IL-1β, IL-8, TNF-α, VEGF, IL-6 and IL-10. With azithromycin treatment, GCF volume decreased significantly on days 2 through 7 (P < 0.05), but increased toward baseline levels on day 14. This was accompanied by a transient decrease in the content of IL-1β, IL-8, TNF-α and VEGF (P < 0.05). IL-6 and IL-10 were not detected. Since plaque was absent throughout the study, the findings suggest that azithromycin produces anti-inflammatory effects in gingiva.
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