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Graft persistence effectively induces and maintains donor-specific unresponsiveness.
J Surg Res. 1997 Mar; 68(2):145-52.JS

Abstract

BACKGROUND

In the present study we attempted to evaluate the role of the graft as an alloantigen in induction and maintenance of donor-specific prolongation of allograft survival by short course(s) of FK506 treatment in rat heart transplantation. Materials and methods. In the WKA/Qdj-to-LEW combination group, FK506 (3 mg/kg/day, 7 days, s.c.) was administered from Day 0 after cardiac transplantation. A second WKA/ Qdj cardiac graft was transplanted on Day 14 into the LEW recipient after removal of the first graft on Day 3 or Day 7. In other groups an additional course of FK506 (3 mg/kg/day, 7 days, s.c.) was given from Day 35. A second WKA/Qdj cardiac graft was transplanted on Day 49 into the LEW recipient after removal of the first graft on Day 7 or Day 28.

RESULTS

A short course of FK506 treatment allowed for survival prolongation of a cardiac allograft [mean survival time (MST) = 42.8 days]. Removal of the first graft on Day 7 (MST = 16.4 days) but not on Day 3 (MST = 10.2 days) caused donor-specific prolongation of the second allograft survival, which was significantly shorter than that in the recipient without the graftectomy (MST = 32.8 days). When graftectomy was performed on Day 3, there were immunohistochemically detectable levels of donor class II expressing cells in the recipient spleen on Day 7, indicating that the presence of the graft more effectively induced unresponsiveness than microchimerism alone. The additional course of FK506 treatment on Day 35 maintained graft survival (MST > 90.6 days). Removal of the first graft on Day 7 (MST = 13.5 days) or Day 28 (MST = 24.7 days) did not show significant prolongation of the second allograft survival, whereas significant survival prolongation of the second graft was observed in the recipient without the graftectomy (MST = 38.8 days). However, marked survival prolongation of the second donor-specific allograft in half of the recipients that had received the second course of FK506 treatment after graftectomy on Day 28 indicates that residual donor antigen can function as tolerizing antigen with an FK506 supplement.

CONCLUSIONS

We concluded that the persistence of a graft more effectively induces and maintains donor-specific unresponsiveness than does the chimeric state of graft-derived cells alone under immunosuppression by FK506 in the rat heart transplantation model.

Authors+Show Affiliations

Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9184673

Citation

Nishinaka, H, et al. "Graft Persistence Effectively Induces and Maintains Donor-specific Unresponsiveness." The Journal of Surgical Research, vol. 68, no. 2, 1997, pp. 145-52.
Nishinaka H, Nakafusa Y, Hirano T, et al. Graft persistence effectively induces and maintains donor-specific unresponsiveness. J Surg Res. 1997;68(2):145-52.
Nishinaka, H., Nakafusa, Y., Hirano, T., Takeda, K., Kawano, R., Nakano, M., Arima, T., Nakamura, K., Kamei, T., & Tanaka, M. (1997). Graft persistence effectively induces and maintains donor-specific unresponsiveness. The Journal of Surgical Research, 68(2), 145-52.
Nishinaka H, et al. Graft Persistence Effectively Induces and Maintains Donor-specific Unresponsiveness. J Surg Res. 1997;68(2):145-52. PubMed PMID: 9184673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Graft persistence effectively induces and maintains donor-specific unresponsiveness. AU - Nishinaka,H, AU - Nakafusa,Y, AU - Hirano,T, AU - Takeda,K, AU - Kawano,R, AU - Nakano,M, AU - Arima,T, AU - Nakamura,K, AU - Kamei,T, AU - Tanaka,M, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 145 EP - 52 JF - The Journal of surgical research JO - J Surg Res VL - 68 IS - 2 N2 - BACKGROUND: In the present study we attempted to evaluate the role of the graft as an alloantigen in induction and maintenance of donor-specific prolongation of allograft survival by short course(s) of FK506 treatment in rat heart transplantation. Materials and methods. In the WKA/Qdj-to-LEW combination group, FK506 (3 mg/kg/day, 7 days, s.c.) was administered from Day 0 after cardiac transplantation. A second WKA/ Qdj cardiac graft was transplanted on Day 14 into the LEW recipient after removal of the first graft on Day 3 or Day 7. In other groups an additional course of FK506 (3 mg/kg/day, 7 days, s.c.) was given from Day 35. A second WKA/Qdj cardiac graft was transplanted on Day 49 into the LEW recipient after removal of the first graft on Day 7 or Day 28. RESULTS: A short course of FK506 treatment allowed for survival prolongation of a cardiac allograft [mean survival time (MST) = 42.8 days]. Removal of the first graft on Day 7 (MST = 16.4 days) but not on Day 3 (MST = 10.2 days) caused donor-specific prolongation of the second allograft survival, which was significantly shorter than that in the recipient without the graftectomy (MST = 32.8 days). When graftectomy was performed on Day 3, there were immunohistochemically detectable levels of donor class II expressing cells in the recipient spleen on Day 7, indicating that the presence of the graft more effectively induced unresponsiveness than microchimerism alone. The additional course of FK506 treatment on Day 35 maintained graft survival (MST > 90.6 days). Removal of the first graft on Day 7 (MST = 13.5 days) or Day 28 (MST = 24.7 days) did not show significant prolongation of the second allograft survival, whereas significant survival prolongation of the second graft was observed in the recipient without the graftectomy (MST = 38.8 days). However, marked survival prolongation of the second donor-specific allograft in half of the recipients that had received the second course of FK506 treatment after graftectomy on Day 28 indicates that residual donor antigen can function as tolerizing antigen with an FK506 supplement. CONCLUSIONS: We concluded that the persistence of a graft more effectively induces and maintains donor-specific unresponsiveness than does the chimeric state of graft-derived cells alone under immunosuppression by FK506 in the rat heart transplantation model. SN - 0022-4804 UR - https://www.unboundmedicine.com/medline/citation/9184673/Graft_persistence_effectively_induces_and_maintains_donor_specific_unresponsiveness_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(97)95053-8 DB - PRIME DP - Unbound Medicine ER -