TY - JOUR
T1 - Donor dendritic cells and recipient Kupffer cells in the induction of donor-specific immune hyporesponsiveness
AU - Nakagawa, K.
AU - Matsuno, T.
AU - Iwagaki, H.
AU - Morimoto, Y.
AU - Fujiwara, T.
AU - Sadamori, H.
AU - Inagaki, M.
AU - Urushihara, N.
AU - Yagi, T.
AU - Tanaka, N.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - The aim of this study was to investigate the ability of portovenously administered donor antigens to induce immune hyporesponsiveness. Lewis (LEW, RT-11) rats received Brown Norway (BN, RT-1n) rat donor splenocytes, via either the portal vein (PV group) or the peripheral vein (IV group). The immune responses of LEW rats, treated with either donor BN or third party Wistar King A (WKA, RT-1k) splenocytes were established by the persistence of donor dendritic cells (DCs) in the host liver measured using fluorescence microscopy and flow cytometry and by the mixed lymphocyte reaction (MLR). The effect of intravenous gadolinium chloride (GDCI3) on the blockade of Kupffer cell function prior to portovenous administration of splenocytes was also assessed. The MLR response was strongly inhibited in a BN-restricted manner after portovenous administration of donor BN splenocytes, but not by venous nor by portovenous administration of WKA splenocytes. Immunosuppression was blocked by pretreatment with GDCI3. The percentage of donor DCs in hepatic non-parenchymal cells (NPCs) was significantly higher in the PV group compared with the IV group. Treatment with GDCI3 decreased the percentage of donor DCs. In addition, cytotoxic T lymphocyte antigen 4 (CTLA4/CD152), which may function as an immune attenuator, was strongly stained, and B7 was weakly stained in recipient liver in the PV group compared with the IV group. These results suggest that both donor DCs and recipient Kupffer cells (self DCs) are involved in the induction of immune hyporesponsiveness by donor cells. This occurs via portovenous administration, in which a signal of the CTLA4-B7 pathway played an important part in inhibiting the interaction of CD28 and its B7 ligands.
AB - The aim of this study was to investigate the ability of portovenously administered donor antigens to induce immune hyporesponsiveness. Lewis (LEW, RT-11) rats received Brown Norway (BN, RT-1n) rat donor splenocytes, via either the portal vein (PV group) or the peripheral vein (IV group). The immune responses of LEW rats, treated with either donor BN or third party Wistar King A (WKA, RT-1k) splenocytes were established by the persistence of donor dendritic cells (DCs) in the host liver measured using fluorescence microscopy and flow cytometry and by the mixed lymphocyte reaction (MLR). The effect of intravenous gadolinium chloride (GDCI3) on the blockade of Kupffer cell function prior to portovenous administration of splenocytes was also assessed. The MLR response was strongly inhibited in a BN-restricted manner after portovenous administration of donor BN splenocytes, but not by venous nor by portovenous administration of WKA splenocytes. Immunosuppression was blocked by pretreatment with GDCI3. The percentage of donor DCs in hepatic non-parenchymal cells (NPCs) was significantly higher in the PV group compared with the IV group. Treatment with GDCI3 decreased the percentage of donor DCs. In addition, cytotoxic T lymphocyte antigen 4 (CTLA4/CD152), which may function as an immune attenuator, was strongly stained, and B7 was weakly stained in recipient liver in the PV group compared with the IV group. These results suggest that both donor DCs and recipient Kupffer cells (self DCs) are involved in the induction of immune hyporesponsiveness by donor cells. This occurs via portovenous administration, in which a signal of the CTLA4-B7 pathway played an important part in inhibiting the interaction of CD28 and its B7 ligands.
KW - Dendritic cells
KW - Gadolinium chloride
KW - Kupffer cells
KW - Tolerance
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U2 - 10.1177/147323000102900209
DO - 10.1177/147323000102900209
M3 - Article
C2 - 11393345
AN - SCOPUS:0035005410
VL - 29
SP - 119
EP - 130
JO - Journal of International Medical Research
JF - Journal of International Medical Research
SN - 0300-0605
IS - 2
ER -