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CD4⁺ T Lymphocytes Are Not Necessary for the Acute Rejection of Vascularized Mouse Lung Transplants¹

Andrew E. Gelman^*, Mikio Okazaki^*, Jiaming Lai^*, Christopher G. Kornfeld^*, Friederike H. Kreisel, Steven B. Richardson^*, Seiichiro Sugimoto^*, Jeremy R. Tietjens^*, G. Alexander Patterson^*, Alexander S. Krupnick^* and Daniel Kreisel^2,*

^* Division of Cardiothoracic Surgery, Department of Surgery, and Department of Pathology and Immunology, Washington University, St. Louis, MO 63110

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ A.E.G. is supported by a grant from The National Heart, Lung, and Blood Institute (1R43HL87456-01). D.K. is supported by a grant jointly sponsored by The National Heart, Lung, and Blood Institute and The Thoracic Surgery Foundation for Research and Education (1K08HL083983-01), by the American Association for Thoracic Surgery John W. Kirklin Research Scholarship, and by a grant from the Roche Organ Transplantation Research Foundation.

² Address correspondence and reprint requests to Dr. Daniel Kreisel, Assistant Professor of Surgery, Pathology & Immunology, Campus Box 8234, 660 South Euclid Avenue, Washington University, St. Louis, MO 63110-1013. E-mail address: kreiseld{at}wudosis.wustl.edu