The role of passenger leukocyte genotype in rejection and acceptance of rat liver allografts.
BACKGROUND
Although graft-resident passenger leukocytes are known to mediate acute rejection by triggering direct allorecognition, they may also act in an immunomodulatory fashion and play an important role in tolerance induction. Our purpose in the current study was to utilize rat bone marrow chimeras to evaluate the role of the genotype of passenger leukocytes in both acute rejection and tolerance of liver allografts.


METHODS
The fate of livers bearing donor-type, recipient-type, and third-party passenger leukocytes was evaluated in the MHC class I and II mismatched rejector combination ACI-->LEW and the acceptor combination PVG-->DA.


RESULTS
We report that although treatment of ACI liver donors with lethal irradiation does not lead to prolongation of graft survival in the ACI-->LEW strain combination, ACI livers bearing recipient-type (LEW) or third-party passenger leukocytes (BN) are rejected at a significantly slower rate. We confirm that lethal irradiation of PVG donor animals leads to abrogation of tolerance induction with acute rejection of their livers by DA recipients. However, the majority of PVG livers carrying donor-type (PVG), recipient-type (DA), or third-party (LEW) passenger leukocytes are accepted for >100 days. These DA recipients develop immune tolerance to the donor parenchyma (PVG).


CONCLUSIONS
Our findings demonstrate that long-term acceptance of liver allografts and tolerance induction is not dependent on the presence of donor-type passenger leukocytes and can be achieved with organs carrying donor-type, recipient-type, or third-party passenger leukocytes. The importance of the MHC framework on the surface of passenger leukocytes as a critical regulator of the immune response after transplantation of chimeric organs is substantiated by the delayed tempo of rejection of ACI livers bearing recipient-type or third-party passenger leukocytes in the ACI-->LEW strain combination.
Kreisel
Daniel
D
Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Petrowsky
Henrik
H
Krasinskas
Alyssa M
AM
Krupnick
Alexander S
AS
Szeto
Wilson Y
WY
McLean
Andrew D
AD
Popma
Sicco H
SH
Gelman
Andrew E
AE
Traum
Marcy K
MK
Furth
Emma E
EE
Moore
Jonni S
JS
Rosengard
Bruce R
BR
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation / Q000379:methods; D005838:Genotype; D006084:Graft Rejection / Q000503:physiopathology*; D006085:Graft Survival / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018183:Transplantation Chimera / Q000502:physiology*; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous