Document Detail


Inhibition of T cell apoptosis in the aqueous humor of patients with uveitis by IL-6/soluble IL-6 receptor trans-signaling.
MedLine Citation:
PMID:  15470075     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A fundamental mechanism of immune privilege in the eye is the induction of T lymphocyte apoptosis. Intraocular inflammation in uveitis implies compromise of immune privilege. This study sought to determine whether apoptosis of T cells is actively inhibited in patients with uveitis and by what pathways this may occur. Apoptotic lymphocytes were found to be absent from aqueous humor (AqH) of virtually all patients with recent-onset uveitis. However, T cells removed from the eye were highly susceptible to both spontaneous and Fas ligand-induced apoptosis in vitro. AqH from patients with uveitis had no modulatory effect on Fas ligand-induced apoptosis, but strongly suppressed survival factor deprivation-induced apoptosis. In contrast, noninflammatory AqH from patients undergoing cataract surgery had no modulatory effects on apoptosis at all. These data suggest that triggering of the Fas pathway is diminished in uveitis, and also that homeostatic resolution through survival factor deprivation-induced apoptosis is inhibited by factors present in AqH. The most widely recognized pathways, common gamma-chain cytokines and type I IFNs, did not contribute to AqH-mediated T cell survival. High levels of both IL-6 and soluble IL-6R were found in AqH. IL-6 alone did not induce T cell survival, because IL-6R expression on T cells in AqH was too low to facilitate signaling. However, combinations of IL-6 and soluble IL-6R were highly effective inhibitors of T cell apoptosis, suggesting that the trans-signaling pathway is likely to be a key mediator of T cell apoptosis inhibition mediated by uveitis AqH.
Authors:
S John Curnow; Dagmar Scheel-Toellner; Will Jenkinson; Karim Raza; Omar M Durrani; Jeff M Faint; Saaeha Rauz; Kaska Wloka; Darrell Pilling; Stefan Rose-John; Christopher D Buckley; Philip I Murray; Mike Salmon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  173     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-07     Completed Date:  2004-11-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5290-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Rheumatology, Medical Research Council Centre for Immune Regulation, Division of Immunity and Infection, Medical School, The University of Birmingham, UK. s.j.curnow@bham.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Antigens, CD95 / physiology
Apoptosis*
Aqueous Humor / immunology*
Humans
Interleukin-6 / physiology*
Middle Aged
Receptors, Interleukin-6 / physiology*
Signal Transduction / physiology*
T-Lymphocytes / physiology*
Uveitis / immunology*
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Interleukin-6; 0/Receptors, Interleukin-6

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