Affiliation:
1. Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, North Carolina 27834
2. Department of Medicine, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina 29425
Abstract
ABSTRACT
T lymphocytes from patients with sarcoidosis respond weakly when stimulated with mitogen or antigen. However, the mechanisms responsible for this anergy are not fully understood. Here, we investigated the protein levels of nuclear transcription factor NF-κB (p50, p65, and p105), IκBα (inhibitor of NF-κB), T-cell receptor (TCR) CD3ζ-chain, tyrosine kinase p56
LCK
, and nuclear factor of activated T cells c2 (NF-ATc2) in peripheral blood CD4
+
T cells from patients with sarcoidosis. Baseline expression of p65 in these lymphocytes was reduced in 50% of patients. The reduced levels of p65 in sarcoid CD4
+
T cells concurred with decreased levels of p50, p105, CD3ζ, p56
LCK
, IκBα, and NF-ATc2. Polyclonal stimulation of NF-κB-deficient sarcoid T cells resulted in reduced expression of CD69 and CD154, decreased proliferation, and cytokine (i.e., interleukin 2 [IL-2] and gamma interferon [IFN-γ]) production. The clinical significance of these findings is suggested by the association between low p65 levels and the development of more severe and active sarcoidosis. Although correlative, our results support a model in which multiple intrinsic signaling defects contribute to peripheral T-cell anergy and the persistence of chronic inflammation in sarcoidosis.
Publisher
American Society for Microbiology
Subject
Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy
Reference75 articles.
1. Aronica, M. A., et al. 1999. Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo. J. Immunol. 163:5116-5124.
2. Immunosuppression by Glucocorticoids: Inhibition of NF-κB Activity Through Induction of IκB Synthesis
3. Baars, P. A., M. M. Maurice, M. Rep, B. Hooibrink, and R. A. van Lier. 1995. Heterogeneity of the circulating human CD4+ T cell population. Further evidence that the CD4+CD45RA−CD27− T cell subset contains specialized primed T cells. J. Immunol. 154:17-25.
4. TCR ζ-chain downregulation: curtailing an excessive inflammatory immune response
5. Control of apoptosis by Rel/NF-κB transcription factors
Cited by
32 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献