title: Immunological study of unresponsive state in rat hepatic transplant model. 2. Immunosuppressive factor in the serum from the tolerant hosts.
abstract: Our previous study demonstrated that Lewis (LEW) rat recipients engrafted with Brown-Norway (BN) rat liver displayed a long-term graft survival and that phenotypic and functional analyses of graft-infiltrating cells on day 6 postgrafting showed a lower proportion and activity of cytotoxic cells in long-term surviving hosts than LEW recipients engrafted with DA rat liver which showed acute rejection on day 9 postgrafting. In order to assess the immunological mechanisms of unresponsiveness, we analyzed the lymphocyte and serum from LEW recipients engrafted with BN liver. Spleen cells from tolerant LEW recipients on day 6 posttransplantation had no suppressor effect on the one-way mixed lymphocyte culture (MLC) reaction. On the other hand, when serum was added to MLC at a concentration of 6% of the total volume, it suppressed the mixed lymphocyte reaction (MLR) toward donor BN cells by 45.6%, but not toward third-party DA stimulator (-0.4%). Adoptive transfer of the serum from tolerant LEW hosts into the virgin secondary LEW hosts significantly prolonged the graft survival of BN kidneys from 7.8 +/- 0.2 to 14.7 +/- 1.6 days (p < 0.01), but not of third party DA kidney graft (mean survival time = 9.5 +/- 1.3 days). The in vitro study demonstrated that the suppressor factor in the serum inhibited the production of IL-2 as well as gamma-IFN in MLR. The suppressor factor was absorbed by LEW cells stimulated with BN cells in vitro, indicating that this factor was directed against recognition sites on responder T lymphocytes. These results showed that an antigen-specific tolerogenic factor which recognized the idiotype of the donor was released into the circulation through the process of BN liver grafting.
authors.affiliation: Second Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Y
authors.initials: Y
authors.lastname: Ohsaka
authors.forename: T
authors.initials: T
authors.lastname: Hamashima
authors.forename: H
authors.initials: H
authors.lastname: Yura
authors.forename: H
authors.initials: H
authors.lastname: Yasuii
authors.forename: T
authors.initials: T
authors.lastname: Oka
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013491:Suppressor Factors, Immunologic / Q000097:blood*
chemical_list: D007376:Interleukin-2; D013491:Suppressor Factors, Immunologic; D007371:Interferon-gamma