Abstract
The role of simultaneous donor-specific transfusion of unprocessed cellular bone marrow (BM) together with solid organ transplantation, a postulated concept to achieve long-term graft acceptance, was investigated in an experimental setting of semiallogeneic transplantation of parental small bowel (SBTx) to F 1 hybrids. The established graft-vs-host (GvH) model revealed that simultaneous transfer of SB/BM substantially enhanced GvH-mediated immune responses in recipient target organs, e.g. skin, gut, and liver. In comparison to isolated SBTx, animal survival decreased from 16.1(± 0.9) to 10.1(± 0.8) days after additional BM transfusion, P < 0.001. Severe tissue injury of GvH-susceptible target organs in the setting of simultaneous SB and BMTx was associated with significant changes in recruitment and tissue distribution of NKR-P1+ cells during the GvH-related proliferative immune response. Tacrolimus effectively suppressed these initial events and prevented recipient animals from clinically and histologically observed damage caused by GvH disease.
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References
Billingham RE, Brent L, Medawar P (1956) Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance. Philos Trans R Soc London SerB 239: 357–412
Slavin S, Strober S, Fuks Z, Kaplan HS (1977) Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice. Long-term survival of allogeneic bone marrow and skin grafts. J Exp Med 146: 34–48
Starzl TE, Demetris AJ, Trucco M, Ramos H, Zeevi A, Rudert WA, Kocova M, Ricordi C, Ildstad S, Murase N (1992) Systemic chimerism in human female recipients of male livers. Lancet 340: 876–877
Starzl TE, Demetris AJ, Trucco M, Zeevi A, Ramos H, Terasaki P, Rudert WA, Kocova M, Ricordi C, Ildstad S, Murase N (1993) Chimerism and donor-specific nonreactivity 27 to 29 years after kidney allotransplantation. Transplantation 55: 1272–1277
Starzl TE, Demetris AJ, Trucco M, Murase N, Ricordi C, Ildstad S, Ramos H, Todo S, Tzakis A, Fung JJ, Nalesnik M, Zeevi A, Rudert WA, Kocova M Cell migration and chimerism after whole organ transplantation: the basis of graft acceptance. Hepatology 17: 1127–1152
Lechler RI, Batchelor JR (1982) Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor-strain dendritic cells. J Exp Med 155: 31–41
Bushell A, Pearson TC, Morris PJ, 13. Wood KJ (1995) Donor-recipient microchimerism is not required for tolerance induction following recipient pretreatment with donor-specific transfusion and anti-CD 4 antibody: Evidence of a clear role for short-term antigen persistence. Transplantation 59: 1367 1371 14.
Schlitt HJ, Hundrieser J, Ringe B, Pichlmayr R (1994) Donor-type microchimerism associated with graft rejection eight years after liver transplantation. N Eng J Med 330: 646–647
Naper C, Vaage JT, Lambracht D, Lovik G, Butcher GW, Wonigeit K, Rolstad B (1995) Alloreactive natural killer 15. cells in the rat: complex genetics of major histocompatibility complex control. Eur J Immunol 25: 1249–1256
Rolstad B, Fossum S, Bazin H, Kimber I, Marshall J, Sparshott SM, Ford WL 16. (1985) The rapid rejection of allogeneic lymphocytes by a non-adaptive, cell-mediated mechanism ( NK activity ). Immunology 54: 127-138
Biassoni R, Ferrini S, Prigione I, Pelak VS, Sekaly RP, Long EO (1991) Acti- 17. vated CD 3 CD 16 + natural killer cells express a subset of the lymphokine genes induced in activated a (3” and y S’ 18. T cells. Scand J Immunol 33: 247-252
Bankhurst AD, Imir T (1989) The mechanisms involved in the activation 19. of human natural killer cells by staphylococcal enterotoxin (I. Cell Immunol 122: 108–122
Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, Romagnani S (1993) Natural killer cell stimulatory factor (interleukin 12[IL12]) induces T helper type 1 (TH I)-specific immune responses and inhibits the development of IL-4 producing cells. J Exp Med 177: 1199–1204
Fändrich F, Waaga AM, Schröder.1, Schweizer E, Schroeder P (1994) Tissue dependent alteration of the MHC-I and -II expression after the use of deoxyspergualin for suppression of the graftversus-host disease in small bowel transplantation. Transplant Proc 26: 1592–1593
Fossum S, Rolstad B (1986) The roles of interdigitating cells (IDC) and natural killer ( NK) cells in the rapid rejection of allogeneic lymphocytes. Eur J Immunol 16: 440-450
Rolstad B, Herberman RB, Reynolds CW (1986) Natural killer cell activity in the rat. V. The circulation patterns and tissue localization of peripheral blood large granular lymphocytes ( LGL ). J Immunol 136: 2800-2809
Coutinho A (1989) Beyond clonal selection and network. Immunol Rev 110: 63–87
Cohen IR (1992) The cognitive paradigm and the immunological homunculus. Immunol Today 13: 490–492
Hansson M, Petersson M, Koo GC, Wigzell H, Kiessling R (1988) In vivo function of natural killer cells as regulators of myeloid precursor cells in the spleen. Eur J Immunol 18: 485–488
Murphy WJ, Kumar V, Bennett M (1987) Acute rejection of murine bone marrow allografts by natural killer cells and T cells. J Exp Med 166: 1499–1509
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Fändrich, F., Jahnke, T., Peters, J., Exner, B., Papachrysanthou, A., Zavazava, N. (1996). Circumvention of natural killer cell and T-cell mediated allogeneic target killing with tacrolimus (FK506) in small bowel transplantation related graft-vs-host disease. In: Mühlbacher, F., et al. Transplant International . Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-00818-8_67
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DOI: https://doi.org/10.1007/978-3-662-00818-8_67
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