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.
Nakano
T
T
Department of Surgery, Liver Transplantation Laboratory, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Kawamoto
S
S
Lai
C-Y
CY
Hsu
L-W
LW
Lin
Y-C
YC
Sasaki
T
T
Aki
T
T
Shigeta
S
S
Goto
T
T
Ohmori
N
N
Sato
S
S
Goto
S
S
Ono
K
K
Chen
C-L
CL
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006657:Histones / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods*; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D023421:Models, Animal; D018448:Models, Immunological; D051381:Rats; D013154:Spleen / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*
D001324:Autoantigens; D006657:Histones; D007074:Immunoglobulin G