Archives of Plastic Surgery

Korean Society of Plastic and Reconstructive Surgeons (대한성형외과학회)
권호 표지

The Effect of Donor Antigen-pulsed Dendritic Cells on Survival of Skin Allograft in a Rat Model

흰쥐 모델에서 공여항원에 감작된 수지상세포가 피부동종이식의 생착에 미치는 영향

  • Eun, Seok Chan (Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine) ;
  • Kim, Byung Jun (Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine) ;
  • Kim, Jin Hee (Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine) ;
  • Heo, Chan Yeong (Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine) ;
  • Baek, Rong Min (Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine) ;
  • Chang, Hak (Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine) ;
  • Minn, Kyung Won (Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine)
  • 은석찬 (서울대학교 의과대학 성형외과학교실) ;
  • 김병준 (서울대학교 의과대학 성형외과학교실) ;
  • 김진희 (서울대학교 의과대학 성형외과학교실) ;
  • 허찬영 (서울대학교 의과대학 성형외과학교실) ;
  • 백롱민 (서울대학교 의과대학 성형외과학교실) ;
  • 장학 (서울대학교 의과대학 성형외과학교실) ;
  • 민경원 (서울대학교 의과대학 성형외과학교실)
  • Received : 2008.01.22
  • Accepted : 2008.04.30
  • Published : 2008.07.10
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Prevention of acute rejection in skin allografts without continuous immunosuppression lacks reports in worldwide literature. Needs for chronic immunosuppression preclude the use of tissue allograft as a routine surgical reconstructive option. Recently dendritic cells(DC) gained considerable attention as antigen presenting cells that are also capable of immunologic tolerance induction. This study assesses the effects of alloantigen-pulsed dendritic cells in induction of survival increase in a rat skin allograft model. Methods: Recipient-derived dendritic cells were harvested from rat whole blood and cultured with GM-CSF(200 ng/mL) and IL-4(8 ng/mL) for 2 weeks. Then donor-specific alloantigen pulsed dendritic cells were reinjected into tail vein before skin graft. The rat dorsal skin allografts were transplanted in 5 subgroups. Groups: I) untreated, II) anti-lymphocyte serum(ALS, 0.5 mL), III) FK-506(2 mg/kg), IV) DCp, VI) DCp and FK-506. Graft appearance challenges were assessed postoperatively. Results: The group V(DC and FK-506 treated) showed longest graft survival rate(23.5 days) than other groups; untreated(5.8 days), ALS(7.2 days), FK-506 (17.5 days), DCp(12.2 days). Conclusion: Donor antigen pulsed host dendritic cell combined with short-term immunosuppression prolong skin allograft survival and has potential therapeutic application for induction of donor antigen specific tolerance.

Keywords

Acknowledgement

Supported by : 한국과학재단

References

  1. White E, Hildeman WH: Allografts in genetically defined rats: difference in survival between kidney and skin. Science 162: 1293, 1968 https://doi.org/10.1126/science.162.3859.1293
  2. Lechler R, Ng WF, Steinman RM: Dendritic cell in transplantation-friend or foe? Immunity 14: 357, 2001 https://doi.org/10.1016/S1074-7613(01)00116-9
  3. Austyn JM, Phil MA: Dendritic cells. Cur Opin Hematol 5: 3, 1998 https://doi.org/10.1097/00062752-199801000-00002
  4. Van Schooten WC, Strang G, Palathumpat V: Biological properties of dendritic cells: implications to their use in the treatment of cancer. Mol Med Today 3: 254, 1997 https://doi.org/10.1016/S1357-4310(97)01047-2
  5. Buttemeyer R, Jones NF, Min Z, Rao U: Rejection of the component tissues of limb allografts in rats immunosuppressed with FK-506 and cyclosporine. Plast Reconstr Surg 97: 139, 1996 https://doi.org/10.1097/00006534-199601000-00023
  6. Hardin CA, Werder AA: A one year study of surviving homografted mouse skin. Plast Reconstr Surg 15: 107, 1955 https://doi.org/10.1097/00006534-195502000-00003
  7. Bilingham RE, Krohn PL, Medawar PB: Effect of cortisone on survival of skin homografts in rabbits. Br Med J 1: 1157, 1951 https://doi.org/10.1136/bmj.1.4716.1157
  8. Goto T, Kino T, Hatanaka, Nishiyama M, Okuhara M, Kohsaka M, Aoki H, Imanaka H: Discovery of FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis. Transplant Proc 19: 4, 1987
  9. Murase N, Starzl TE, Demetris AJ, Valdivia L, Tanabe M, Cramer D, Makowka L: Hamster-to-rat heart and liver xenotransplantation with FK-506 plus antiproliferative drugs. Transplantation 55: 701, 1993 https://doi.org/10.1097/00007890-199304000-00003
  10. Romani N, Gruner S, Brang D, Kampgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G: Proliferation dendritic cell progenitors in human blood. J Exp Med 180: 83, 1994 https://doi.org/10.1084/jem.180.1.83
  11. Billingham RE, Brent L, Medawar PB: Actively acquired tolerance of foreign cells. Transplantation 76: 1409, 2003 https://doi.org/10.1097/01.TP.0000102675.72061.88
  12. Starzl TE, Demetris AJ, Trucco M, Ramos H, Zeevi A, Rudert WA, Kocova M, Ricordi C, Ildstad S, Murase N: Systemic chimerism in human female recipients of male livers. Lancet 340: 876, 1992 https://doi.org/10.1016/0140-6736(92)93286-V
  13. Lee JE, Kang HK, Seoung EY, Yang SH, Kim SJ, Shin SJ, Kim YS, Lee JS, Kim S: The effects of maturation resistant donor dendritic cells on alloimmune response in mice. Korean J Nephrol 24: 514, 2005
  14. Coates PT, Thomson AW: Dendritic cells, tolerance induction and transplant outcome. Am J Transplant 2: 299, 2002 https://doi.org/10.1034/j.1600-6143.2002.20403.x
  15. Nguyen VT, Taieb A, Sacks JM, Unadkat JV, Clavijo JA, Kim H, Feili-Hariri M, Lee WP: Allopeptide- pulsed dendritic cells and composite tissue allograft survival. Microsurgery 27: 105, 2007 https://doi.org/10.1002/micr.20314