Type V collagen-induced oral tolerance plus low-dose cyclosporine prevents rejection of MHC class I and II incompatible lung allografts

Yoshito Yamada, Yasuo Sekine, Shigetoshi Yoshida, Kazuhiro Yasufuku, Irina Petrache, Heather L. Benson, David D. Brand, Ichiro Yoshino, David S. Wilkes

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Autoimmunity to type V collagen (col(V)) is a major risk factor for lung allograft rejection. Although col(V)-induced oral tolerance abrogates rejection of minor histoincompatible lung transplants, its ability to prevent rejection of fully MHC incompatible lung allografts is unknown. Rat lung allografts fully incompatible at MHC class I and II loci (Brown Norway (RT1n)) were transplanted into untreated Wistar Kyoto rat recipients (WKY, RT1l), or WKY rats were fed col(V) pretransplantation. To determine whether col(V) enhanced cyclosporine (CsA)-mediated immune suppression, WKY rats were treated with low-dose CsA (5 mg/kg), post-transplant, or oral col(V) plus CsA. The data showed that in contrast to col(V) or CsA, col(V) plus low-dose CsA significantly prevented rejection pathology, down-regulated alloantigen-induced production of IFN-γ and IL-17A, and suppressed chemotaxis for lung macrophages in allograft bronchoalveolar lavage fluid that was associated with lower local levels of MCP-1 (CCL2). Col(V) plus CsA was associated with alloantigen-induced expression of IL-10 in mediastinal lymph node or splenic T cells, intragraft expression of IL-10 and Foxp3 in perivascular and peribronchiolar mononuclear cells, and constitutive production of IL-10 from allograft alveolar macrophages. These data demonstrate that col(V) enhances low-dose CsA-mediated immune suppression, and suggest a role for oral col(V) in immune modulation in lung transplantation.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalJournal of Immunology
Volume183
Issue number1
DOIs
StatePublished - Jul 1 2009

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Collagen Type V
Cyclosporine
Allografts
Inbred WKY Rats
Lung
Interleukin-10
Isoantigens
Transplants
Aptitude
Lung Transplantation
Interleukin-17
Bronchoalveolar Lavage Fluid
Alveolar Macrophages
Chemotaxis
Norway
Autoimmunity
Lymph Nodes
Macrophages
Rejection (Psychology)
Pathology

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Type V collagen-induced oral tolerance plus low-dose cyclosporine prevents rejection of MHC class I and II incompatible lung allografts. / Yamada, Yoshito; Sekine, Yasuo; Yoshida, Shigetoshi; Yasufuku, Kazuhiro; Petrache, Irina; Benson, Heather L.; Brand, David D.; Yoshino, Ichiro; Wilkes, David S.

In: Journal of Immunology, Vol. 183, No. 1, 01.07.2009, p. 237-245.

Research output: Contribution to journalArticle

Yamada, Yoshito ; Sekine, Yasuo ; Yoshida, Shigetoshi ; Yasufuku, Kazuhiro ; Petrache, Irina ; Benson, Heather L. ; Brand, David D. ; Yoshino, Ichiro ; Wilkes, David S. / Type V collagen-induced oral tolerance plus low-dose cyclosporine prevents rejection of MHC class I and II incompatible lung allografts. In: Journal of Immunology. 2009 ; Vol. 183, No. 1. pp. 237-245.
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