Tacrolimus Pretreatment Attenuates Preexisting Xenospecific Immunity and Abrogates Hyperacute Rejection in a Presensitized Hamster to Rat Liver Transplant Model

Overview

Journal Transplantation

Specialty General Surgery

Date 1996 Jun 27

PMID 8685952

Authors

M Tsugita

L A Valdivia

A S Rao

F Pan

S Celli

A J Demetris

J J Fung

T E Starzl

Affiliations

Soon will be listed here.

Abstract

In the hamster to rat liver transplant model, we determined the efficacy of tacrolimus in attenuating natural xenospecific humoral immunity and in abrogating the hyperacute liver rejection that is produced by presensitizing the Lewis rat recipient. Hamster livers, transplanted orthotopically into naive rats (controls), were rejected with animal death after 6.4.+/- 0.5 (SD) days. The infusion on (day -6) of 1.5 x 10(7) hamster hepatocytes, or of 1.5 x 10(8) nonparenchymal cells (NPC), resulted in hyperacute rejection and death in < or = 1.9 days. However, when the rats were pretreated with 1 mg/kg/day tacrolimus from days -6 to -1, survival of non-presensitized animals was prolonged to 25 +/- 20 days and that of recipients presensitized with hamster hepatocytes to 36 +/- l6 days or with NPC to 32 +/- 1.7 days. The tacrolimus pretreatment significantly reduced the hamster-specific complement-dependent cytotoxic antibodies response directed to liver NPC but not to lymph node cell targets. These observations suggest that the prolongation of survival by appropriately timed treatment with this T cell directed drug model is caused by the inhibition of humoral as well as cellular xenograft rejection.

References

Thomas F, Marchman W, Carobbi A, Araneda D, Pryor W, Thomas J . Immunobiology of the xenograft response: xenograft rejection in immunodeficient animals. Transplant Proc. 1991; 23(1 Pt 1):208-9. View

Barker C, Billingham R . Histocompatibility requirements of heart and skin grafts in rats. Transplant Proc. 1971; 3(1):172-5. View

Nardo B, Valdivia L, Pan F, Celli S, Tsugita M, Demetris A . Pretransplant xenogeneic blood transfusion combined with FK 506 prolongs hamster-to-rat liver xenograft survival. Transplant Proc. 1994; 26(3):1208. PMC: 2974300. View

McGregor D, Gowans J . THE ANTIBODY RESPONSE OF RATS DEPLETED OF LYMPHOCYTES BY CHRONIC DRAINAGE FROM THE THORACIC DUCT. J Exp Med. 2009; 117(2):303-20. PMC: 2137611. DOI: 10.1084/jem.117.2.303. View

Galili U, Rachmilewitz E, Peleg A, FLECHNER I . A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J Exp Med. 1984; 160(5):1519-31. PMC: 2187506. DOI: 10.1084/jem.160.5.1519. View

Coutinho A . The theory of the 'one nonspecific signal' model for b cell activation. Transplant Rev. 1975; 23:49-65. DOI: 10.1111/j.1600-065x.1975.tb00148.x. View

Galili U, Buehler J, SHOHET S, Macher B . The human natural anti-Gal IgG. III. The subtlety of immune tolerance in man as demonstrated by crossreactivity between natural anti-Gal and anti-B antibodies. J Exp Med. 1987; 165(3):693-704. PMC: 2188289. DOI: 10.1084/jem.165.3.693. View

Lim S, Wee A, Chong S, White D . An analysis of concordant xenograft rejection in the nude rat model. Transplant Proc. 1990; 22(5):2095-6. View

Seglen P . Preparation of isolated rat liver cells. Methods Cell Biol. 1976; 13:29-83. DOI: 10.1016/s0091-679x(08)61797-5. View

10.

Valdivia L, Demetris A, Fung J, Celli S, Murase N, Starzl T . Successful hamster-to-rat liver xenotransplantation under FK506 immunosuppression induces unresponsiveness to hamster heart and skin. Transplantation. 1993; 55(3):659-61. PMC: 2976608. View

11.

Hayakawa K, Hardy R . Normal, autoimmune, and malignant CD5+ B cells: the Ly-1 B lineage?. Annu Rev Immunol. 1988; 6:197-218. DOI: 10.1146/annurev.iy.06.040188.001213. View

12.

Galili U, Macher B, Buehler J, SHOHET S . Human natural anti-alpha-galactosyl IgG. II. The specific recognition of alpha (1----3)-linked galactose residues. J Exp Med. 1985; 162(2):573-82. PMC: 2187733. DOI: 10.1084/jem.162.2.573. View

13.

Chaussy C, Hammer C, von Scheel J, Eisenberger F, Pielsticker K, Brendel W . Experimental xenogeneic kidney transplantation in closely related species. Transplantation of cat kidneys to untreated and sensitized dogs. Res Exp Med (Berl). 1973; 159(4):266-75. DOI: 10.1007/BF01851601. View

14.

Wu G, Cramer D, Chapman F, Oriol R, Makowka L . Genetic control of the humoral immune response to xenografts. I. Functional characterization of rat monoclonal antibodies to hamster heart xenografts. Transplantation. 1995; 60(12):1497-503. DOI: 10.1097/00007890-199560120-00022. View

15.

Fujii H, Takada T, Nemoto K, Abe F, Fujii A, Takeuchi T . In vitro immunosuppressive properties of spergualins to murine T cell response. J Antibiot (Tokyo). 1989; 42(5):788-94. DOI: 10.7164/antibiotics.42.788. View

16.

Tsugita M, Rao A, Sun H, Wakizaka Y, Madariaga J, Pan F . Pretreatment of recipients (nude rat) with donor antigens leads to prolonged survival of hamster heart xenografts. Transplant Proc. 1996; 28(2):696-7. PMC: 2975611. View

17.

Perper R, Najarian J . Experimental renal heterotransplantion. II. Closely related species. Transplantation. 1966; 4(6):700-12. DOI: 10.1097/00007890-196611000-00005. View

18.

Starzl T, Ishikawa M, Putnam C, Porter K, Picache R, Husberg B . Progress in and deterrents to orthotopic liver transplantation, with special reference to survival, resistance to hyperacute rejection, and biliary duct reconstruction. Transplant Proc. 1974; 6(4 Suppl 1):129-39. PMC: 3004363. View

19.

Kaplan E, Dresdale A, Diehl J, Aronovitz M, Konstam M, Katzen N . Donor-specific transfusion and cardiac xenografts. Transplantation. 1988; 46(4):605-7. DOI: 10.1097/00007890-198810000-00034. View

20.

Murase N, Starzl T, Demetris A, Valdivia L, Tanabe M, Cramer D . Hamster-to-rat heart and liver xenotransplantation with FK506 plus antiproliferative drugs. Transplantation. 1993; 55(4):701-7; discussion 707-8. PMC: 2957097. DOI: 10.1097/00007890-199304000-00003. View