Inhibition of chronic rejection by antibody induced vascular accommodation in fully allogeneic heart allografts.
BACKGROUND
The potential role of altered antibody responses as an effector protective mechanism to induce graft accommodation has been widely investigated in xenogeneic responses. Here we investigate the protective effects of antibody binding to vascular endothelium in a fully mismatched allogeneic model of heart transplantation.


METHODS
ACI recipients of WF cardiac grafts were treated either with allochimeric [alpha1h ]-RT1.A class I major histocompatibility complex (MHC) extracts (1 mg/rat, p.v. day 0) or high dose of CsA (10 mg/kg/day, p.o., day 0-6). Cardiac allografts were evaluated at 100 days posttransplant by immunohistology for evidence of chronic rejection and/or vascular accommodation. Activation of apoptotic or antiapoptotic mechanisms was verified by DNA fragmentation (TUNEL) analysis.


RESULTS
Allochimeric therapy resulted in inhibition of chronic rejection, absence of neointimal formation and induction of vascular accommodation of fully allogeneic WF hearts in ACI hosts. Such accommodation was evident by IgG and IgM vascular endothelial binding and marked reduction of DNA fragmentation. In contrast, CsA therapy resulted in marked neointimal proliferation, without evidence of vascular accommodation. Immunohistochemical analysis failed to demonstrate vascular endothelial antibody binding. Further, severe chronic rejection following CsA treatment was accompanied by marked DNA fragmentation.


CONCLUSIONS
Alteration of humoral immunity induces vascular accommodation in allogeneic transplantation. Vascular accommodation is the underlying mechanism for inhibition allograft vasculopathy following allochimeric MHC class I therapy.
Semiletova
Natalya V
NV
The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-7054, USA.
Shen
Xiu-Da
XD
Baibakov
Boris
B
Feldman
Daniel M
DM
Mukherjee
Kaushik
K
Frank
Jonathan M
JM
Stepkowski
Stainslaw M
SM
Busuttil
Ronald W
RW
Kupiec-Weglinski
Jerzy W
JW
Ghobrial
Rafik M
RM
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D017209:Apoptosis / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007165:Immunosuppression Therapy / Q000379:methods*; D007518:Isoantibodies / Q000032:analysis; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies