Transplant International pp 275-280 | Cite as
In vivo depletion of NKR-P1 positive cells in the recipient prior to small bowel transplantation enhances graft-versus-host disease (GvHD) in the rat
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Abstract
Recent evidence for major histocompatibility complex (MHC) class I antigen-directed recognition mechanisms of natural killer cells (NKs) have revived interests in investigating non-adaptive immune responses in the framework of solid organ transplantation. A semiallogeneic rat model of heterotopic small bowel transplantation (HSBTx) from male DA parental to male F1 hybrid rats (DA x LEW) was established to investigate the role of host NKs to attenuate graftversus-host (GvH)-mediated immunosuppression and tissue injury. By use of anti-NKR-P1 monoclonal antibody (mAb) 3.2.3, host NKs were depleted effectively in vivo after triple intraperitoneal injection prior to HSBTx. In contrast to non-depleted animals, an initial lack of NK activity in F1 hosts significantly decreased the mean survival (P < 0.01) and substantially enhanced graftversus-host disease (GvHD)-related damage to lymphoid and non-lymphoid target organs. These findings emphasize the important immunoregulatory role of host NKs during the early onset of GvHD.
Key words
Graft-versus-host disease (GvHD) Allogeneic lymphocyte cytotoxicity Natural killer cells Small bowel transplantation Major histocompatibility complex (MHC)Preview
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References
- 1.Trinchieri G (1990) Biology of natural killer cells. Adv Immunol 47: 187–376CrossRefGoogle Scholar
- 2.Colonna M, Brooks EG, Falco M, Ferrara GB, Strominger JL (1993) Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. Science 260: 1121–1124PubMedCrossRefGoogle Scholar
- 3.Moretta L, Ciccone E, Mingari MC, Biassoni R, Moretta A (1994) Human natural killer cells: origin, clonality, specificity and receptors. Adv Immunol 55: 341–380PubMedCrossRefGoogle Scholar
- 4.Vaage JT, Naper C, Lovik G, Lam-bracht D, Rehm A, Hedrich HJ, Wonigeit K, Rolstad B (1994) Control of rat natural killer cell-mediated allorecognition by a major histocompatibility complex region encoding nonclassical class I antigens. J Exp Med 180: 641–651PubMedCrossRefGoogle Scholar
- 5.Naper C, Vaage JT, Lambracht D, Lovik G, Butcher GW, Wonigeit K, Rolstad B (1995) Alloreactive natural killer cells in the rat: complex genetics of major histocompatibility complex control. Eur J Immunol 25: 1249–1256PubMedCrossRefGoogle Scholar
- 6.Yokoyama WM, Seaman WE (1993) The Ly-49 and NKR-P1 gene families encoding lectin-like receptors on natural killer cells: the NK gene complex. Annu Rev Immunol 11: 613–635PubMedCrossRefGoogle Scholar
- 7.Chambers WH, Adamkiewicz T, Hou-chins JP (1993) Type II integral membrane proteins with characteristics of C-type animal lectins expressed by natural killer ( NK) cells. Glycobiology 3: 9–14Google Scholar
- 8.Karlhofer FM, Ribaudo RK, Yokoyama WM (1992) MHC class I alloantigen specificity of Ly-49’ IL-2-activated natural killer cells. Nature 358: 66–70PubMedCrossRefGoogle Scholar
- 9.Ford WL, Rolstad B, Fossum S (1984) The elimination of allogeneic lymphocytes: a useful model of natural killer cell activity in vivo? Immunol Today 5: 227–228CrossRefGoogle Scholar
- 10.Rolstad B, Fossum S, Bazin H, Kimber I, Marshall J, Sparshott SM, Ford WL (1985) The rapid rejection of allogeneic lymphocytes by a non-adaptive, cell-mediated mechanism ( NK activity ). Immunology 54: 127–138Google Scholar
- 11.Kiessling R, Hochman PS, Haller O, Shearer GM, Wigzell H, Cudkowicz G (1977) Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts. Eur J Immunol 7: 655–663PubMedCrossRefGoogle Scholar
- 12.Cudkowicz G, Stimpfling JH (1964) Deficient growth of C57BL marrow cells transplanted in F1 hybrid mice. Association with the histocompatibility-2 locus. Immunology 7: 291–306PubMedGoogle Scholar
- 13.Chambers WH, Vujanovic NL, DeLeo AB, Olszowy MW, Herberman RB, Hiserodt JC (1989) Monoclonal antibody to a triggering structure expressed on rat natural killer cells and adherent lymphokine-activated killer cells. J Exp Med 169: 1373–1389PubMedCrossRefGoogle Scholar
- 14.Van den Brink MRM, Hunt LE, Hiserodt JC (1990) In vivo treatment with monoclonal antibody 3.2.3 selectively eliminates natural killer cells in rats. J Exp Med 171: 197–210PubMedCrossRefGoogle Scholar
- 15.Fändrich F, Waaga AM, Schröder J, 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: 1592–1593Google Scholar
- 16.Sviland L, Pearson ADJ, Green MA, Eastham EJ, Malcolm AJ, Proctor SJ, Hamilton PJ, and the Newcastle Bone Marrow Transplant Group (1989) Expression of MHC class I and II antigens by keratinocytes and enterocytes in acute graft-versus-host disease. Bone Marrow Transplant 4: 233–238PubMedGoogle Scholar
- 17.Hakim FT, Sharrow SO, Payne S, Shearer GM (1991) Repopulation of host lymphohematopoietic systems by donor cells during graft-versus-host reaction in unirradiated adult F1 mice injected with parental lymphocytes. J Immunol 146: 2108–2115PubMedGoogle Scholar
- 18.Romagnani S (1992) Induction of Thl and Th2 responses: a key role for the “natural” immune response? Immunol Today 13: 379–381PubMedCrossRefGoogle Scholar