Peripheral donor leukocytes prolong survival of rat renal allografts.
BACKGROUND
The development of strategies to enhance the survival of transplanted organs and to potentially lower or even discontinue immunosuppressive therapy would represent a significant advancement in post-transplant patient care.


METHODS
We studied the effect of pretransplant infusion of donor leukocytes alone or in combination with a short course of cyclosporine on the long-term outcome of a rat model of kidney allograft.


RESULTS
A single intravenous infusion of donor peripheral blood leukocytes (100x10(6) cells) from Brown-Norway (BN) rats into major histocompatibility complex (MHC) incompatible Lewis recipients largely failed to prolong kidney allograft viability from the same donor transplanted 60, 40, or 30 days after cell infusion. A short course of cyclosporine (per se, unable to prolong graft survival) was started at the same day of donor leukocyte infusion, but instead was able to prolong the survival of the BN kidney transplant-performed 40 days later-but not of a Wistar Furth (WF) third party, with some animals even developing tolerance. A mixed lymphocyte reaction of host cells from long-term surviving rats to BN stimulator cells was significantly reduced as compared with controls. Donor BN DNA was detected in the peripheral blood of Lewis rats until day 40 after BN leukocyte infusion. Microchimerism persisted (60 to 70 days post-transplant) in most long-term graft recipients. Reducing the time interval between donor leukocyte infusion and subsequent kidney transplant to 10 days still prolonged graft survival. Donor peripheral blood mononuclear cells, but not polymorphonuclear cells, in the leukocyte preparation contributed to prolong kidney allograft survival.


CONCLUSIONS
Pretransplant donor leukocyte infusion under the appropriate conditions can tip the immune balance toward improved graft acceptance. This result could be relevant to the achievement of donor-specific tolerance of the graft with the maintenance of an intact response to third-party antigens.
Noris
M
M
Department of Immunology and Clinics of Organ Transplantation, Ospedali Riuniti Bergamo--Mario Negri Institute for Pharmacological Research, Bergamo, Italy. noris@irfmn.mnegri.it
Azzollini
N
N
Mister
M
M
Pezzotta
A
A
Piccinini
G
G
Casiraghi
F
F
Cugini
D
D
Perico
N
N
Orisio
S
S
Remuzzi
G
G
D000818:Animals; D001483:Base Sequence; D002678:Chimera / Q000235:genetics / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage; D004247:DNA / Q000235:genetics; D006082:Graft Enhancement, Immunologic / Q000379:methods*; D006085:Graft Survival / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology*; D017708:Leukocyte Transfusion; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D012689:Sequence Homology, Nucleic Acid; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D004247:DNA