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Published in: Transplant International 8/2003

01-08-2003 | Original Article

Induction of indirect donor-specific hyporesponsiveness by transportal RT1-peptide pulse in rat skin transplantation

Authors: Masao Yamamura, Takahito Yagi, Hiromi Iwagaki, Naoshi Mitsuoka, Liu Jie, Sun Dong Sheng, Hiroaki Matsuda, Hiroshi Sadamori, Masaru Inagaki, Noriaki Tanaka

Published in: Transplant International | Issue 8/2003

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Abstract

In the present study, we examined whether transportal pulse of class I major histocompatibility complex (MHC) allopeptides can induce indirect (non-chimeric) donor-specific hyporesponsiveness, using a high-responder rat skin transplantation model. Two donor-specific 8-amino acid peptides corresponding to residues 58–65 and 70–77 in the α1 helical region of RT1.Aa were synthesized. In order to test immunogenicity of these peptides, mixed lymphocyte reaction (MLR) was performed. Then, 100-μg portions of peptides were injected into recipient Lewis (LEW, RT1.Al) rats via the portal vein 14 days before skin transplantation. Skin allografts from August Copenhagen Irish (ACI, RT1a) or Wistar King A (WKA, RT1k, third-party) donors were transplanted to LEW (RT1l) recipients. Transportal pulse of residues 58–65 and 70–77 prolonged graft survival significantly in ACI-to-LEW skin transplantation (17.6±0.40 and 18.0±0.45 days) compared with control (14.2±0.37 days). However, pulse of residues 106–113, a non-donor-specific control, did not prolong graft survival time (14.6±0.40 days) in the same combination. Regarding the third-party donor, residues 58–65 injected into LEW recipients had no effect on survival time of skin grafts (19.0±0.84 days) derived from WKA donors compared with the untreated WKA-to-LEW control (19.4±0.93 days). Transportal pulse of RT1.Aa peptides induced donor-specific hyporesponsiveness even in a high-responder rat skin transplantation model. Our results suggest that graft enhancement by transportal exposure to donor cells may not be induced by a chimeric process but, instead, by an indirect mechanism not involving intervention of viable donor cells.
Literature
1.
go back to reference Chowdhury NC, Murphy B, Sayegh MH, Jing MX, Roy DK, Hardy MA, Oluwole SF (1996) Acquired systemic tolerance to rat cardiac allografts induced by intrathymic inoculation of synthetic polymorphic MHC class I allopeptides. Transplantation 62:1878–1882PubMed Chowdhury NC, Murphy B, Sayegh MH, Jing MX, Roy DK, Hardy MA, Oluwole SF (1996) Acquired systemic tolerance to rat cardiac allografts induced by intrathymic inoculation of synthetic polymorphic MHC class I allopeptides. Transplantation 62:1878–1882PubMed
2.
go back to reference Didlake R, Kim EK, Kahan BD (1988) Ability of 3M KCl-extracted histocompatibility antigen to potentiate the immunosuppressive effect of cyclosporine to prolong the survival of heterotopic cardiac allografts. Transplantation 46:743–747PubMed Didlake R, Kim EK, Kahan BD (1988) Ability of 3M KCl-extracted histocompatibility antigen to potentiate the immunosuppressive effect of cyclosporine to prolong the survival of heterotopic cardiac allografts. Transplantation 46:743–747PubMed
3.
go back to reference Fandrich F, Zhu X, Schroder J, Dresske B, Henne-Bruns D, Oswald H, Zavazava N (1999) Different in vivo tolerogenicity of MHC class I peptides. J Leukoc Biol 65:16–27PubMed Fandrich F, Zhu X, Schroder J, Dresske B, Henne-Bruns D, Oswald H, Zavazava N (1999) Different in vivo tolerogenicity of MHC class I peptides. J Leukoc Biol 65:16–27PubMed
4.
go back to reference Florence LS, Ito T, Ang KK, Jiang GL, Wong CS, Goto S, Didlake R, Kim EK, Stepkowski S, Kahan BD (1989) The synergistic effect of total-lymphoid irradiation with extracted donor alloantigen in inducing transplantation unresponsiveness. Transplantation 47:156–162PubMed Florence LS, Ito T, Ang KK, Jiang GL, Wong CS, Goto S, Didlake R, Kim EK, Stepkowski S, Kahan BD (1989) The synergistic effect of total-lymphoid irradiation with extracted donor alloantigen in inducing transplantation unresponsiveness. Transplantation 47:156–162PubMed
5.
go back to reference Gill TJ III, Kunz HW, Misra DN, Hassett AL (1987) The major histocompatibility complex of the rat. Transplantation 43:773–785 Gill TJ III, Kunz HW, Misra DN, Hassett AL (1987) The major histocompatibility complex of the rat. Transplantation 43:773–785
6.
go back to reference Goto S, Stepkowski S, Kahan BD (1992) Benefit of multiple over single doses of 3M KCl-extracted histocompatibility antigen in the potentiating cyclosporine-induced prolongation of rat cardiac allograft survival. Transplantation 53:705–707PubMed Goto S, Stepkowski S, Kahan BD (1992) Benefit of multiple over single doses of 3M KCl-extracted histocompatibility antigen in the potentiating cyclosporine-induced prolongation of rat cardiac allograft survival. Transplantation 53:705–707PubMed
7.
go back to reference Hamashima T, Stepkowski SM, Smith S, Kahan BD (1994) Induction of transplantation tolerance by a single intrathymic injection of 3M KCl-extracted donor histocompatibility antigens combined with two doses of anti-rat α/β-T cell receptor monoclonal antibodies. Transplantation 58:105–107PubMed Hamashima T, Stepkowski SM, Smith S, Kahan BD (1994) Induction of transplantation tolerance by a single intrathymic injection of 3M KCl-extracted donor histocompatibility antigens combined with two doses of anti-rat α/β-T cell receptor monoclonal antibodies. Transplantation 58:105–107PubMed
8.
go back to reference Hanaway MJ, Geissler EK, Wang J, Fechner JH Jr, Buelow R, Knechtle SJ (1996) Immunosuppressive effects of an HLA class I-derived peptide in a rat cardiac allograft model. Transplantation 61:1222–1228PubMed Hanaway MJ, Geissler EK, Wang J, Fechner JH Jr, Buelow R, Knechtle SJ (1996) Immunosuppressive effects of an HLA class I-derived peptide in a rat cardiac allograft model. Transplantation 61:1222–1228PubMed
9.
go back to reference Ishido N, Matsuoka J, Matsuno T, Nakagawa K, Tanaka N (1999) Induction of donor-specific hyporesponsiveness and prolongation of cardiac allograft survival by jejunal administration of donor splenocytes. Transplantation 68:1377–1382PubMed Ishido N, Matsuoka J, Matsuno T, Nakagawa K, Tanaka N (1999) Induction of donor-specific hyporesponsiveness and prolongation of cardiac allograft survival by jejunal administration of donor splenocytes. Transplantation 68:1377–1382PubMed
10.
go back to reference Ito T, Stepkowski S, Kahan BD (1990) Soluble antigen and cyclosporine-induced specific unresponsiveness in rats. Frequency of alloantigen-specific T cytotoxic cells in normal, sensitized, and unresponsive rats. Transplantation 49:422–428PubMed Ito T, Stepkowski S, Kahan BD (1990) Soluble antigen and cyclosporine-induced specific unresponsiveness in rats. Frequency of alloantigen-specific T cytotoxic cells in normal, sensitized, and unresponsive rats. Transplantation 49:422–428PubMed
11.
go back to reference Jin T, Toki J, Inaba M, Sugiura K, Fan T, Yu C, Lian Z, Takase K, Feng B, Ito T, Cui Y, Yang G, Ikehara S (2001) A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed by injection of donor bone marrow cells via portal vein. Transplantation 71:1725–1731PubMed Jin T, Toki J, Inaba M, Sugiura K, Fan T, Yu C, Lian Z, Takase K, Feng B, Ito T, Cui Y, Yang G, Ikehara S (2001) A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed by injection of donor bone marrow cells via portal vein. Transplantation 71:1725–1731PubMed
12.
go back to reference Liang J, Yamaguchi Y, Matsuda T, Ohshiro H, Zhang JL, Okabe K, Matsumura F, Ishihara K, Uchino S, Mori K, Yamada S, Ogawa M (2000) Posttransplant infusion of donor-specific blood induces immunological unresponsiveness in rat hepatic allografts. Transplantation 70:1363–1371PubMed Liang J, Yamaguchi Y, Matsuda T, Ohshiro H, Zhang JL, Okabe K, Matsumura F, Ishihara K, Uchino S, Mori K, Yamada S, Ogawa M (2000) Posttransplant infusion of donor-specific blood induces immunological unresponsiveness in rat hepatic allografts. Transplantation 70:1363–1371PubMed
13.
go back to reference Munn DH, Pressey J, Beall AC, Hudes R, Alderson MR (1996) Selective activation-induced apoptosis of peripheral T cells imposed by macrophages. J Immunol 156:523–532PubMed Munn DH, Pressey J, Beall AC, Hudes R, Alderson MR (1996) Selective activation-induced apoptosis of peripheral T cells imposed by macrophages. J Immunol 156:523–532PubMed
14.
go back to reference Nisco S, Vriens P, Hoyt G, Lyu SC, Farfan F, Pouletty P, Krensky AM, Clayberger C (1994) Induction of allograft tolerance in rats by an HLA class-I-derived peptide and cyclosporin A. J Immunol 152:3786–3792PubMed Nisco S, Vriens P, Hoyt G, Lyu SC, Farfan F, Pouletty P, Krensky AM, Clayberger C (1994) Induction of allograft tolerance in rats by an HLA class-I-derived peptide and cyclosporin A. J Immunol 152:3786–3792PubMed
15.
go back to reference Odorico JS, Barker CF, Posselt AM, Naji A (1992) Induction of donor-specific tolerance to rat cardiac allografts by intrathymic inoculation of bone marrow. Surgery 112:370–377PubMed Odorico JS, Barker CF, Posselt AM, Naji A (1992) Induction of donor-specific tolerance to rat cardiac allografts by intrathymic inoculation of bone marrow. Surgery 112:370–377PubMed
16.
go back to reference Odorico JS, Posselt AM, Naji A, Markmann JF, Barker CF (1993) Promotion of rat cardiac allograft survival by intrathymic inoculation of donor splenocytes. Transplantation 55:1104–1107PubMed Odorico JS, Posselt AM, Naji A, Markmann JF, Barker CF (1993) Promotion of rat cardiac allograft survival by intrathymic inoculation of donor splenocytes. Transplantation 55:1104–1107PubMed
17.
go back to reference Oluwole SF, Chowdhury NC, Jin MX, Hardy MA (1993) Induction of transplantation tolerance to rat cardiac allografts by intrathymic inoculation of allogeneic soluble peptides. Transplantation 56:1523–1527PubMed Oluwole SF, Chowdhury NC, Jin MX, Hardy MA (1993) Induction of transplantation tolerance to rat cardiac allografts by intrathymic inoculation of allogeneic soluble peptides. Transplantation 56:1523–1527PubMed
18.
go back to reference Perloff LJ, Barker CF (1984) Variable response to donor-specific blood transfusion in the rat. Transplantation 38:178–182PubMed Perloff LJ, Barker CF (1984) Variable response to donor-specific blood transfusion in the rat. Transplantation 38:178–182PubMed
19.
go back to reference Rada C, Lorenzi R, Powis SJ, Bogaerde J van den, Parham P, Howard JC (1990) Concerted evolution of class I genes in the major histocompatibility complex of murine rodents. Proc Natl Acad Sci U S A 87:2167–2171PubMed Rada C, Lorenzi R, Powis SJ, Bogaerde J van den, Parham P, Howard JC (1990) Concerted evolution of class I genes in the major histocompatibility complex of murine rodents. Proc Natl Acad Sci U S A 87:2167–2171PubMed
20.
go back to reference Salgar SK, Sawai H, Kunz HW, Gill TJ III (1994) Cloning and expression of the rat class I MHC gene RT1.Al. Immunogenetics 39:447PubMed Salgar SK, Sawai H, Kunz HW, Gill TJ III (1994) Cloning and expression of the rat class I MHC gene RT1.Al. Immunogenetics 39:447PubMed
21.
go back to reference Sayegh MH, Khoury SJ, Hancock WW, Weiner HL (1992) Induction of immunity and oral tolerance with polymorphic class II major histocompatibility complex allopeptides in the rat. Proc Natl Acad Sci USA 89:7762–7766PubMed Sayegh MH, Khoury SJ, Hancock WW, Weiner HL (1992) Induction of immunity and oral tolerance with polymorphic class II major histocompatibility complex allopeptides in the rat. Proc Natl Acad Sci USA 89:7762–7766PubMed
22.
go back to reference Sayegh MH, Zhang ZJ, Hancock WW, Kwok CA, Carpenter CB, Weiner HL (1992) Down-regulation of the immune response to histocompatibility antigens and prevention of sensitization by skin allografts by orally administered alloantigen. Transplantation 53:163–166PubMed Sayegh MH, Zhang ZJ, Hancock WW, Kwok CA, Carpenter CB, Weiner HL (1992) Down-regulation of the immune response to histocompatibility antigens and prevention of sensitization by skin allografts by orally administered alloantigen. Transplantation 53:163–166PubMed
23.
go back to reference Sayegh MH, Khoury SJ, Hancock WW, Weiner HL, Carpenter CB (1993) Induction of immunity and oral tolerance to alloantigen by polymorphic class II major histocompatibility complex allopeptides in the rat. Transplant Proc 25:357–358 Sayegh MH, Khoury SJ, Hancock WW, Weiner HL, Carpenter CB (1993) Induction of immunity and oral tolerance to alloantigen by polymorphic class II major histocompatibility complex allopeptides in the rat. Transplant Proc 25:357–358
24.
go back to reference Stepkowski SM, Yu J, Kahan BD (1999) Induction of tolerance by oral administration of a tolerogenic allochimeric donor/recipient class I MHC protein. Transplant Proc 31:1557 Stepkowski SM, Yu J, Kahan BD (1999) Induction of tolerance by oral administration of a tolerogenic allochimeric donor/recipient class I MHC protein. Transplant Proc 31:1557
25.
go back to reference Wang M, Stepkowski SM, Yu J, Wang M, Kahan BD (1997) Localization of cryptic tolerogenic epitopes in the α1-helical region of the RT1.Au alloantigen. Transplantation 63:1373–1379PubMed Wang M, Stepkowski SM, Yu J, Wang M, Kahan BD (1997) Localization of cryptic tolerogenic epitopes in the α1-helical region of the RT1.Au alloantigen. Transplantation 63:1373–1379PubMed
26.
go back to reference Wasowska B, Baldwin WM, Howell DN, Sanfilippo F (1991) The effects of donor-specific blood transfusion enhancement of rat renal allografts on cytotoxic activity and phenotypes of peripheral blood lymphocytes, splenocytes, and graft-infiltrating cells. Transplantation 51:451–459PubMed Wasowska B, Baldwin WM, Howell DN, Sanfilippo F (1991) The effects of donor-specific blood transfusion enhancement of rat renal allografts on cytotoxic activity and phenotypes of peripheral blood lymphocytes, splenocytes, and graft-infiltrating cells. Transplantation 51:451–459PubMed
27.
go back to reference Wood ML, Monaco AP, Gottschalk R (1991) Characterization of spleen cells capable of inducing unresponsiveness in ALS-treated mice. Transplantation 51:208–213PubMed Wood ML, Monaco AP, Gottschalk R (1991) Characterization of spleen cells capable of inducing unresponsiveness in ALS-treated mice. Transplantation 51:208–213PubMed
28.
go back to reference Yasumura T, Kahan BD (1983) Prolongation of rat kidney allografts by pretransplant administration of donor antigen extract or whole blood transfusion combined with a short course of cyclosporine. Transplantation 36:603–609PubMed Yasumura T, Kahan BD (1983) Prolongation of rat kidney allografts by pretransplant administration of donor antigen extract or whole blood transfusion combined with a short course of cyclosporine. Transplantation 36:603–609PubMed
29.
go back to reference Yoshimura N, Kahan BD (1985) Nature of the suppressor cells mediating prolonged graft survival after administration of extracted histocompatibility antigen and cyclosporine. Transplantation 39:162–168PubMed Yoshimura N, Kahan BD (1985) Nature of the suppressor cells mediating prolonged graft survival after administration of extracted histocompatibility antigen and cyclosporine. Transplantation 39:162–168PubMed
30.
go back to reference Zavazava N, Fandrich F, Zhu X, Freese A, Behrens D, Yoo-Ott KA (2000) Oral feeding of an immunodominant MHC donor-derived synthetic class I peptide prolongs graft survival of heterotopic cardiac allografts in a high-responder rat strain combination. J Leukoc Biol 67:793–800PubMed Zavazava N, Fandrich F, Zhu X, Freese A, Behrens D, Yoo-Ott KA (2000) Oral feeding of an immunodominant MHC donor-derived synthetic class I peptide prolongs graft survival of heterotopic cardiac allografts in a high-responder rat strain combination. J Leukoc Biol 67:793–800PubMed
Metadata
Title
Induction of indirect donor-specific hyporesponsiveness by transportal RT1-peptide pulse in rat skin transplantation
Authors
Masao Yamamura
Takahito Yagi
Hiromi Iwagaki
Naoshi Mitsuoka
Liu Jie
Sun Dong Sheng
Hiroaki Matsuda
Hiroshi Sadamori
Masaru Inagaki
Noriaki Tanaka
Publication date
01-08-2003
Publisher
Springer-Verlag
Published in
Transplant International / Issue 8/2003
Print ISSN: 0934-0874
Electronic ISSN: 1432-2277
DOI
https://doi.org/10.1007/s00147-002-0496-8

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