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Lipopolysaccharide stimulated hepatic stellate cells enhance the proliferation of regulatory T cells in a contact dependent manner
Author(s) -
Dangi Anil,
Sumpter Tina L,
Thomson Angus W,
Gandhi Chandrashekhar R
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.366.6
Mechanisms of the remarkable immunological tolerance of liver allograft across MHC barrier are inadequately understood. Levels of endotoxin (lipopolysaccharide, LPS), which strongly influences immune system, are increased pre‐ and post‐transplantation. LPS stimulates the centrally located hepatic stellate cells (HSC) to release several immunoreactive cytokines/chemokines. We hypothesized that LPS‐stimulated HSC play an important role in liver allograft tolerance by influencing tolerogenic regulatory T cells (Treg). LPS increased expression of MHCII and co‐stimulatory molecules CD80 and CD86 on HSC. In co‐culture, LPS (1‐100 ng/ml)‐stimulated HSC caused proliferation of allogeneic CD4+CD25highCD127low T cells in a contact‐dependent manner, similar to that by anti‐CD3/CD28. In contrast, LPS/HSC inhibited activation, and induced apoptosis of conventional T cells via ICOS and Fas activation. Furthermore, LPS/HSC‐Treg interaction caused decrease in the levels of inflammatory cytokines and chemokines released by HSC. Our results indicate that HSC plays an important role liver allograft acceptance by expanding Treg while concurrently eliminating immunogenic T cells. (Support: NIH PO1A1081678)