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PMID: 9730890 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Antiinflammatory effects of CD95 ligand (FasL)-induced apoptosis.

The Journal of experimental medicine ·Vol. 188 ·No. 5 ·1998-09-07 ·Pages 887-96

Gao Y, Herndon JM, Zhang H, Griffith TS, Ferguson TA

Abstract

Apoptosis is critical to homeostasis of multicellular organisms. In immune privileged sites such as the eye, CD95 ligand (FasL)-induced apoptosis controls dangerous inflammatory reactions that can cause blindness. Recently, we demonstrated that apoptotic cell death of inflammatory cells was a prerequisite for the induction of immune deviation after antigen presentation in the eye. In this report, we examine the mechanism by which this takes place. Our results show that Fas- mediated apoptosis of lymphoid cells leads to rapid production of interleukin (IL)-10 in these cells. The apoptotic cells containing IL-10 are responsible for the activation of immune deviation through interaction with antigen-presenting cells (APC). In support of this, we found that apoptotic cells from IL-10(+/+) animals fed to APC in vitro promote Th2 cell differentiation, whereas apoptotic IL-10(-/-) cells, as well as nonapoptotic cells, favor Th1 induction. Thus, apoptotic cell death and tolerance are linked through the production of an antiinflammatory cytokine to prevent dangerous and unwanted immune responses that might compromise organ integrity.

MeSH Terms
Animals Anterior Chamber/immunology,metabolism Antigen Presentation Apoptosis/immunology Cell Differentiation/immunology Fas Ligand Protein Inflammation/immunology,prevention & control Interleukin-10/biosynthesis,genetics Interleukin-4/genetics Ligands Membrane Glycoproteins/physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Th2 Cells/cytology,metabolism fas Receptor/physiology
Chemicals
Fas Ligand Protein Fasl protein, mouse Ligands Membrane Glycoproteins fas Receptor Interleukin-10 Interleukin-4
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Gao Y
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Herndon J M
Zhang H
Griffith T S
Ferguson T A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.188.5.887
Published
1998-09-07
Pages
887-96
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213381
Subset
IM
Grants
NEI NIH HHS · EY06765 · United States
NEI NIH HHS · EY08972 · United States
External Links
PubMed source DOI: 10.1084/jem.188.5.887 PMC Full Text View journal details
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