Endotoxin down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells

Citation
Pa. Knolle et al., Endotoxin down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells, J IMMUNOL, 162(3), 1999, pp. 1401-1407
Citations number
45
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
162
Issue
3
Year of publication
1999
Pages
1401 - 1407
Database
ISI
SICI code
0022-1767(19990201)162:3<1401:EDTCAB>2.0.ZU;2-B
Abstract
Endotoxin is physiologically present in portal venous blood at concentratio ns of 100 pg/ml to 1 ng/ml. Clearance of endotoxin from portal blood occurs through sinusoidal lining cells, i.e., Kupffer cells, and liver sinusoidal endothelial cells (LSEC). We have recently shown that LSEC are fully effic ient APCs, Here, we studied the influence of endotoxin on the accessory fun ction of LSEC, Incubation of Ag-presenting LSEC with physiological concentr ations of endotoxin lead to greater than or equal to 80% reduction of the a ccessory function, measured by release of IFN-gamma from CD4(+) T cells. In contrast, conventional APC populations rather showed an increase of the ac cessory function after endotoxin treatment. Inhibition of the accessory fun ction in LSEC by endotoxin was not due to lack of soluble costimulatory sig nals, because neither supplemental IL-1 beta, IL-2, IFN-gamma, or IL-12 cou ld rescue the accessory function, Ag uptake was not influenced by endotoxin in LSEC, However, we found that endotoxin led to alkalinization of the end osomal/lysomal compartment specifically in LSEC but not in bone marrow macr ophages, which indicated that Ag processing, i.e., proteolytic cleavage of protein Ags into peptide fragments, was affected by endotoxin, Furthermore, endotoxin treatment downregulated surface expression of constitutively exp ressed MHC class II, CD80, and CD86. In conclusion, it is conceivable that endotoxin does not alter the clearance function of LSEC to remove gut-deriv ed Ags from portal blood but specifically affects Ag processing and express ion of the accessory molecules in these cells, Consequently, Ag-specific im mune responses by CD4(+) T cells are efficiently down-regulated in the hepa tic microenvironment.