NDLI: CD3Î¶-chain expression of human T lymphocytes is regulated by TNF via Src-like adaptor protein-dependent proteasomal degradation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cope, Andrew P. Falus, András Buzás, Edit I. Matkó, János Nagy, György Balogh, Andrea Érsek, Barbara Molnár, Viktor
Description	Country affiliation: Hungary Author Affiliation: Érsek B ( Department of Genetics, Cell, and Immunobiology, Faculty of Medicine, Semmelweis University, 1089 Budapest, Hungary.)
Abstract	Decreased expression of the TCR Î¶-chain has been reported in several autoimmune, inflammatory, and malignant diseases, suggesting that Î¶-chain downregulation is common at sites of chronic inflammation. Although Î¶-chain is critically important in T lymphocyte activation, the mechanism of the decreased Î¶-chain expression is less clear. Src-like adaptor protein (SLAP) is a master regulator of T cell activation; previous data have reported that SLAP regulates immunoreceptor signaling. We have examined the mechanism and the functional consequences of CD3 Î¶-chain downregulation. TNF treatment of human T lymphocytes (15-40 ng/ml) selectively downregulates CD3 Î¶-chain expression in a dose-dependent manner (p < 0.05) and decreases activation-induced IL-2 expression (p < 0.01). Although blocking of the lysosomal compartment fails to restore TNF-induced CD3 Î¶-chain downregulation, inhibition of the proteasome prevented the effect of TNF. Both SLAP expression and the colocalization of SLAP with CD3 Î¶-chain was enhanced by TNF treatment (p < 0.05 and p < 0.01, respectively), whereas TNF-induced Î¶-chain downregulation was inhibited by gene silencing of SLAP with small interfering RNA. SLAP levels of the CD4(+) T lymphocytes isolated from patients with rheumatoid arthritis were more than 2-fold higher than that of the healthy donors' (p < 0.05); moreover, TNF treatment did not alter the SLAP expression of the CD4(+) cells of anti-TNF therapy-treated patients. Our present data suggest that TNF modulates T cell activation during inflammatory processes by regulating the amount of CD3 Î¶-chain expression via a SLAP-dependent mechanism. These data provide evidence for SLAP-dependent regulation of CD3 Î¶-chain in the fine control of TCR signaling.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adaptor Proteins, Signal Transducing Immunology Antigens, Cd3 Biosynthesis Lymphocyte Activation Proteasome Endopeptidase Complex Metabolism Proto-oncogene Proteins Pp60(c-src) T-lymphocytes Tumor Necrosis Factor-alpha Arthritis, Rheumatoid Blotting, Western Enzyme-linked Immunosorbent Assay Flow Cytometry Gene Expression Regulation Jurkat Cells Microscopy, Confocal Real-time Polymerase Chain Reaction Receptors, Antigen, T-cell Reverse Transcriptase Polymerase Chain Reaction Transfection Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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