TY - JOUR
T1 - Cross-presentation of antigen by diverse subsets of murine liver cells
AU - Ebrahimkhani, Mohammad R.
AU - Mohar, Isaac
AU - Crispe, Ian N.
PY - 2011/10
Y1 - 2011/10
N2 - Antigen cross-presentation is a principal function of specialized antigen-presenting cells of bone marrow origin such as dendritic cells. Although these cells are sometimes known as "professional" antigen-presenting cells, nonbone marrow-derived cells may also act as antigen-presenting cells. Here, using four-way liver cell isolation and parallel comparison of candidate antigen-presenting cells, we show that, depending on the abundance of antigen-donor cells, different subsets of liver cells could cross-present a hepatocyte-associated antigen. This function was observed in both liver sinusoidal endothelial cells and Kupffer cells even at very low antigen concentration, as well as when using soluble protein. Antigen cross-presentation by liver cells induced efficient CD8+ T-cell proliferation in a similar manner to classical dendritic cells from spleen. However, proliferated cells expressed a lower level of T-cell activation markers and intracellular interferon-gamma levels. In contrast to classical spleen dendritic cells, cross-presentation by liver antigen-presenting cells was predominantly dependent on intercellular adhesion molecule-1. Conclusion: Hepatic sinusoids are an environment rich in antigen cross-presenting activity. However, the liver's resident antigen-presenting cells cause partial T-cell activation. These results clarify how the liver can act as a primary site of CD8+ T-cell activation, and why immunity against hepatocyte pathogens is sometimes ineffective.
AB - Antigen cross-presentation is a principal function of specialized antigen-presenting cells of bone marrow origin such as dendritic cells. Although these cells are sometimes known as "professional" antigen-presenting cells, nonbone marrow-derived cells may also act as antigen-presenting cells. Here, using four-way liver cell isolation and parallel comparison of candidate antigen-presenting cells, we show that, depending on the abundance of antigen-donor cells, different subsets of liver cells could cross-present a hepatocyte-associated antigen. This function was observed in both liver sinusoidal endothelial cells and Kupffer cells even at very low antigen concentration, as well as when using soluble protein. Antigen cross-presentation by liver cells induced efficient CD8+ T-cell proliferation in a similar manner to classical dendritic cells from spleen. However, proliferated cells expressed a lower level of T-cell activation markers and intracellular interferon-gamma levels. In contrast to classical spleen dendritic cells, cross-presentation by liver antigen-presenting cells was predominantly dependent on intercellular adhesion molecule-1. Conclusion: Hepatic sinusoids are an environment rich in antigen cross-presenting activity. However, the liver's resident antigen-presenting cells cause partial T-cell activation. These results clarify how the liver can act as a primary site of CD8+ T-cell activation, and why immunity against hepatocyte pathogens is sometimes ineffective.
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U2 - 10.1002/hep.24508
DO - 10.1002/hep.24508
M3 - Article
C2 - 21721032
AN - SCOPUS:80053309337
SN - 0270-9139
VL - 54
SP - 1379
EP - 1387
JO - Hepatology
JF - Hepatology
IS - 4
ER -