RRC ID 179
Author Nakano T, Kawamoto S, Lai CY, Hsu LW, Lin YC, Sasaki T, Aki T, Shigeta S, Goto T, Ohmori N, Sato S, Goto S, Ono K, Chen CL.
Title Characterization of immunosuppressive factors expressed in serum by rat tolerogenic liver transplantation.
Journal Transplant. Proc.
Abstract BACKGROUND:In a rat tolerogenic model of orthotopic liver transplantation (OLT), recipient serum after OLT (post-OLT serum) possesses strong immunosuppressive activity. This study aimed to identify immunosuppressive factors present in early post-OLT serum.
METHODS:Immunosuppressive activity was evaluated in vitro by inhibition of the mixed-lymphocyte reaction (MLR). Autoantigens recognized by MLR-inhibitory IgG were identified by the internal protein sequencing.
RESULTS:Recipient post-OLT serum inhibited MLR, and OLT-inducible IgG was the major immunosuppressive factor. IgG from post-OLT sera (2 to 3 weeks) specifically reacted to 31; 34; and 73-kd autoantigens on spleen cells. The internal sequences of the 31- and 34-kd antigens coincided completely with those of histone H1 molecules. Immunodepletion of anti-histone H1 antibodies (Abs) from early post-OLT serum abolished the MLR-inhibitory activity. Furthermore, rabbit polyclonal Ab-directed histone H1 not only significantly suppressed rat and human MLR but also prolonged survival of heart allografts. Flow-cytometric analysis revealed that some live PVG splenocytes were stained with antihistone H1 Abs, and that these positive cells increased on Con A stimulation. Western blot analysis indicated that several cross-reactive antigens against anti-histone H1 Abs were found in their membrane fraction.
CONCLUSIONS:In this study we provide evidence that autoreactive Abs, against histone H1 are a major OLT-induced graft survival factor, and may play at least a part in overcoming the acute rejection phase to establish solid allograft tolerance.
Volume 37(1)
Pages 80-1
Published 2005-1
DOI 10.1016/j.transproceed.2004.12.290
PII S0041-1345(04)01748-8
PMID 15808554
MeSH Animals Autoantigens / immunology Heart Transplantation / immunology* Histones / immunology Immunoglobulin G / blood Immunoglobulin G / immunology Immunosuppression / methods* Liver Transplantation / immunology* Lymphocyte Culture Test, Mixed Models, Animal Models, Immunological Rats Spleen / immunology Transplantation Tolerance / immunology*
IF 0.806
Times Cited 12