Promotion of skin graft tolerance across MHC barriers by mobilization of dendritic cells in donor hemopoietic cell infusions

Masatoshi Eto, Holger Hackstein, Katsuhiko Kaneko, Kikuo Nomoto, Angus W. Thomson

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Fit3 ligand (FL) dramatically increases the number of immunostimulatory dendritic cells (DC) and their precursors in bone marrow (BM) and secondary lymphoid tissues. Herein we tested the ability of FL-mobilized donor hemopoietic cells to promote induction of skin graft tolerance across full MHC barriers. C57BL/10 (B10; H2b, IE-) mice were given 108 spleen cells (SC) from normal or FL-treated, H-2-mismatched B10.D2 (H2d, IE+) donors i.v. on day 0, 200 mg/kg i.p. cyclophosphamide on day 2, and 107 T cell-depleted BM cells from B10.D2 mice on day 3. B10.D2 skin grafting was performed on day 14. Indefinite allograft survival (100 days) was induced in recipients of FL-SC, but not in mice given normal SC. Tolerance was associated with blood macrochimerism and was confirmed by second-set skin grafting with donor skin 100 days after the first graft. In tolerant mice, peripheral donor-reactive T cells expressing TCR Vβ11 were deleted selectively. Immunocompetence of tolerant FL-SC-treated mice was proven by rapid rejection of third-party skin grafts. To our knowledge this is the first report that mobilization of DC in donor cell infusions can be used to induce skin graft tolerance across MHC barriers, accompanied by specific deletion of donor-reactive T cells.

Original languageEnglish
Pages (from-to)2390-2396
Number of pages7
JournalJournal of Immunology
Volume169
Issue number5
DOIs
Publication statusPublished - Sep 1 2002
Externally publishedYes

Fingerprint

Transplantation Tolerance
Dendritic Cells
Skin
Ligands
Spleen
Skin Transplantation
T-Lymphocytes
Transplants
Immunocompetence
Lymphoid Tissue
Bone Marrow Cells
Cyclophosphamide
Allografts
Bone Marrow

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Promotion of skin graft tolerance across MHC barriers by mobilization of dendritic cells in donor hemopoietic cell infusions. / Eto, Masatoshi; Hackstein, Holger; Kaneko, Katsuhiko; Nomoto, Kikuo; Thomson, Angus W.

In: Journal of Immunology, Vol. 169, No. 5, 01.09.2002, p. 2390-2396.

Research output: Contribution to journalArticle

Eto, Masatoshi ; Hackstein, Holger ; Kaneko, Katsuhiko ; Nomoto, Kikuo ; Thomson, Angus W. / Promotion of skin graft tolerance across MHC barriers by mobilization of dendritic cells in donor hemopoietic cell infusions. In: Journal of Immunology. 2002 ; Vol. 169, No. 5. pp. 2390-2396.
@article{ebbe7182567346eab164baadbba5c862,
title = "Promotion of skin graft tolerance across MHC barriers by mobilization of dendritic cells in donor hemopoietic cell infusions",
abstract = "Fit3 ligand (FL) dramatically increases the number of immunostimulatory dendritic cells (DC) and their precursors in bone marrow (BM) and secondary lymphoid tissues. Herein we tested the ability of FL-mobilized donor hemopoietic cells to promote induction of skin graft tolerance across full MHC barriers. C57BL/10 (B10; H2b, IE-) mice were given 108 spleen cells (SC) from normal or FL-treated, H-2-mismatched B10.D2 (H2d, IE+) donors i.v. on day 0, 200 mg/kg i.p. cyclophosphamide on day 2, and 107 T cell-depleted BM cells from B10.D2 mice on day 3. B10.D2 skin grafting was performed on day 14. Indefinite allograft survival (100 days) was induced in recipients of FL-SC, but not in mice given normal SC. Tolerance was associated with blood macrochimerism and was confirmed by second-set skin grafting with donor skin 100 days after the first graft. In tolerant mice, peripheral donor-reactive T cells expressing TCR Vβ11 were deleted selectively. Immunocompetence of tolerant FL-SC-treated mice was proven by rapid rejection of third-party skin grafts. To our knowledge this is the first report that mobilization of DC in donor cell infusions can be used to induce skin graft tolerance across MHC barriers, accompanied by specific deletion of donor-reactive T cells.",
author = "Masatoshi Eto and Holger Hackstein and Katsuhiko Kaneko and Kikuo Nomoto and Thomson, {Angus W.}",
year = "2002",
month = "9",
day = "1",
doi = "10.4049/jimmunol.169.5.2390",
language = "English",
volume = "169",
pages = "2390--2396",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Promotion of skin graft tolerance across MHC barriers by mobilization of dendritic cells in donor hemopoietic cell infusions

AU - Eto, Masatoshi

AU - Hackstein, Holger

AU - Kaneko, Katsuhiko

AU - Nomoto, Kikuo

AU - Thomson, Angus W.

PY - 2002/9/1

Y1 - 2002/9/1

N2 - Fit3 ligand (FL) dramatically increases the number of immunostimulatory dendritic cells (DC) and their precursors in bone marrow (BM) and secondary lymphoid tissues. Herein we tested the ability of FL-mobilized donor hemopoietic cells to promote induction of skin graft tolerance across full MHC barriers. C57BL/10 (B10; H2b, IE-) mice were given 108 spleen cells (SC) from normal or FL-treated, H-2-mismatched B10.D2 (H2d, IE+) donors i.v. on day 0, 200 mg/kg i.p. cyclophosphamide on day 2, and 107 T cell-depleted BM cells from B10.D2 mice on day 3. B10.D2 skin grafting was performed on day 14. Indefinite allograft survival (100 days) was induced in recipients of FL-SC, but not in mice given normal SC. Tolerance was associated with blood macrochimerism and was confirmed by second-set skin grafting with donor skin 100 days after the first graft. In tolerant mice, peripheral donor-reactive T cells expressing TCR Vβ11 were deleted selectively. Immunocompetence of tolerant FL-SC-treated mice was proven by rapid rejection of third-party skin grafts. To our knowledge this is the first report that mobilization of DC in donor cell infusions can be used to induce skin graft tolerance across MHC barriers, accompanied by specific deletion of donor-reactive T cells.

AB - Fit3 ligand (FL) dramatically increases the number of immunostimulatory dendritic cells (DC) and their precursors in bone marrow (BM) and secondary lymphoid tissues. Herein we tested the ability of FL-mobilized donor hemopoietic cells to promote induction of skin graft tolerance across full MHC barriers. C57BL/10 (B10; H2b, IE-) mice were given 108 spleen cells (SC) from normal or FL-treated, H-2-mismatched B10.D2 (H2d, IE+) donors i.v. on day 0, 200 mg/kg i.p. cyclophosphamide on day 2, and 107 T cell-depleted BM cells from B10.D2 mice on day 3. B10.D2 skin grafting was performed on day 14. Indefinite allograft survival (100 days) was induced in recipients of FL-SC, but not in mice given normal SC. Tolerance was associated with blood macrochimerism and was confirmed by second-set skin grafting with donor skin 100 days after the first graft. In tolerant mice, peripheral donor-reactive T cells expressing TCR Vβ11 were deleted selectively. Immunocompetence of tolerant FL-SC-treated mice was proven by rapid rejection of third-party skin grafts. To our knowledge this is the first report that mobilization of DC in donor cell infusions can be used to induce skin graft tolerance across MHC barriers, accompanied by specific deletion of donor-reactive T cells.

UR - http://www.scopus.com/inward/record.url?scp=0036721798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036721798&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.169.5.2390

DO - 10.4049/jimmunol.169.5.2390

M3 - Article

C2 - 12193706

AN - SCOPUS:0036721798

VL - 169

SP - 2390

EP - 2396

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -