CD4+ T Lymphocytes Are Not Necessary for the Acute Rejection of Vascularized Mouse Lung Transplants

Acute rejection continues to present a major obstacle to successful lung transplantation. Although CD4(+) T lymphocytes are critical for the rejection of some solid organ grafts, the role of CD4(+) T cells in the rejection of lung allografts is largely unknown. In this study, we demonstrate in a nov...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2008-04, Vol.180 (7), p.4754-4762
Main Authors: Gelman, Andrew E, Okazaki, Mikio, Lai, Jiaming, Kornfeld, Christopher G, Kreisel, Friederike H, Richardson, Steven B, Sugimoto, Seiichiro, Tietjens, Jeremy R, Patterson, G. Alexander, Krupnick, Alexander S, Kreisel, Daniel
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Antigen-Presenting Cells - cytology
Antigen-Presenting Cells - immunology
Autoantigens - immunology
B7-1 Antigen - immunology
CD28 Antigens - immunology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Graft Rejection - immunology
Hematopoiesis - immunology
Lung Transplantation - immunology
Lung Transplantation - pathology
Male
Mice
Neovascularization, Physiologic
Transplantation, Homologous - immunology
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Summary:Acute rejection continues to present a major obstacle to successful lung transplantation. Although CD4(+) T lymphocytes are critical for the rejection of some solid organ grafts, the role of CD4(+) T cells in the rejection of lung allografts is largely unknown. In this study, we demonstrate in a novel model of orthotopic vascularized mouse lung transplantation that acute rejection of lung allografts is independent of CD4(+) T cell-mediated allorecognition pathways. CD4(+) T cell-independent rejection occurs in the absence of donor-derived graft-resident hematopoietic APCs. Furthermore, blockade of the CD28/B7 costimulatory pathways attenuates acute lung allograft rejection in the absence of CD4(+) T cells, but does not delay acute rejection when CD4(+) T cells are present. Our results provide new mechanistic insight into the acute rejection of lung allografts and highlight the importance of identifying differences in pathways that regulate the rejection of various organs.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.180.7.4754