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Phosphatidylserine regulates the maturation of human dendritic cells. J Immunol 2004 Sep 01;173(5):2985-94

Date

08/24/2004

Pubmed ID

15322157

DOI

10.4049/jimmunol.173.5.2985

Scopus ID

2-s2.0-4344597636   89 Citations

Abstract

Phosphatidylserine (PS), which is exposed on the surface of apoptotic cells, has been implicated in immune regulation. However, the effects of PS on the maturation and function of dendritic cells (DCs), which play a central role in both immune activation and regulation, have not been described. Large unilamellar liposomes containing PS or phosphatidylcholine were used to model the plasma membrane phospholipid composition of apoptotic and live cells, respectively. PS liposomes inhibited the up-regulation of HLA-ABC, HLA-DR, CD80, CD86, CD40, and CD83, as well as the production of IL-12p70 by human DCs in response to LPS. PS did not affect DC viability directly but predisposed DCs to apoptosis in response to LPS. DCs exposed to PS had diminished capacity to stimulate allogeneic T cell proliferation and to activate IFN-gamma-producing CD4(+) T cells. Exogenous IL-12 restored IFN-gamma production by CD4(+) T cells. Furthermore, activated CTLs proliferated poorly to cognate Ag presented by DCs exposed to PS. Our findings suggest that PS exposure provides a sufficient signal to inhibit DC maturation and to modulate adaptive immune responses.

Author List

Chen X, Doffek K, Sugg SL, Shilyansky J

Author

Xiao Chen MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Apoptosis
CD8-Positive T-Lymphocytes
Cell Differentiation
Cell Division
Dendritic Cells
Humans
Interferon-gamma
Interleukin-12
Lipopolysaccharides
Liposomes
Membrane Glycoproteins
Phosphatidylserines
Protein Subunits
Receptors, Cell Surface
T-Lymphocytes
Toll-Like Receptors