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2016 ; 13
(3
): 277-92
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Modulation of liver tolerance by conventional and nonconventional
antigen-presenting cells and regulatory immune cells
#MMPMID27041638
Horst AK
; Neumann K
; Diehl L
; Tiegs G
Cell Mol Immunol
2016[May]; 13
(3
): 277-92
PMID27041638
show ga
The liver is a tolerogenic organ with exquisite mechanisms of immune regulation
that ensure upkeep of local and systemic immune tolerance to self and foreign
antigens, but that is also able to mount effective immune responses against
pathogens. The immune privilege of liver allografts was recognized first in pigs
in spite of major histo-compatibility complex mismatch, and termed the "liver
tolerance effect". Furthermore, liver transplants are spontaneously accepted with
only low-dose immunosuppression, and induce tolerance for non-hepatic
co-transplanted allografts of the same donor. Although this immunotolerogenic
environment is favorable in the setting of organ transplantation, it is
detrimental in chronic infectious liver diseases like hepatitis B or C, malaria,
schistosomiasis or tumorigenesis, leading to pathogen persistence and weak
anti-tumor effects. The liver is a primary site of T-cell activation, but it
elicits poor or incomplete activation of T cells, leading to their abortive
activation, exhaustion, suppression of their effector function and early death.
This is exploited by pathogens and can impair pathogen control and clearance or
allow tumor growth. Hepatic priming of T cells is mediated by a number of local
conventional and nonconventional antigen-presenting cells (APCs), which promote
tolerance by immune deviation, induction of T-cell anergy or apoptosis, and
generating and expanding regulatory T cells. This review will focus on the
communication between classical and nonclassical APCs and lymphocytes in the
liver in tolerance induction and will discuss recent insights into the role of
innate lymphocytes in this process.