Reference - Detail
|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.|
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.
|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*|
|WOS Category||SURGERY TRANSPLANTATION IMMUNOLOGY|