HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nozaki, T. Articles by Fairchild, R. L. Search for Related Content PubMed PubMed Citation Articles by Nozaki, T. Articles by Fairchild, R. L.

Antibody-Mediated Rejection of Cardiac Allografts in CCR5-Deficient Recipients¹

Taiji Nozaki^2,*,, Hiroyuki Amano^2,*,, Alice Bickerstaff^¶, Charles G. Orosz^¶, Andrew C. Novick^*, Kazunari Tanabe and Robert L. Fairchild^3,*,,

^* Glickman Urological Institute and Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; Department of Urology, Tokyo Women’s Medical School, Tokyo, Japan; and ^¶ Department of Surgery, Transplantation Division, The Ohio State University College of Medicine, Columbus, OH 43210

Rejected MHC-mismatched cardiac allografts in CCR5^–/– recipients have low T cell infiltration, but intense deposition of C3d in the large vessels and capillaries of the graft, characteristics of Ab-mediated rejection. The roles of donor-specific Ab and CD4 and CD8 T cell responses in the rejection of complete MHC-mismatched heart grafts by CCR5^–/– recipients were directly investigated. Wild-type C57BL/6 and B6.CCR5^–/– (H-2^b) recipients of A/J (H-2^a) cardiac allografts had equivalent numbers of donor-reactive CD4 T cells producing IFN-, whereas CD4 T cells producing IL-4 were increased in CCR5^–/– recipients. Numbers of donor-reactive CD8 T cells producing IFN- were reduced 60% in CCR5^–/– recipients. Day 8 posttransplant serum titers of donor-specific Ab were 15- to 25-fold higher in CCR5^–/– allograft recipients, and transfer of this serum provoked cardiac allograft rejection in RAG-1^–/– recipients within 14 days, whereas transfer of either serum from wild-type recipients or immune serum from CCR5-deficient recipients diluted to titers observed in wild-type recipients did not mediate this rejection. Wild-type C57BL/6 and B6.CCR5^–/– recipients rejected A/J cardiac grafts by day 11, whereas rejection was delayed (day 12–60, mean 21 days) in µMT^–/–/CCR5^–/– recipients. These results indicate that the donor-specific Ab produced in CCR5^–/– heart allograft recipients is sufficient to directly mediate graft rejection, and the absence of recipient CCR5 expression has differential effects on the priming of alloreactive CD4 and CD8 T cells.

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 This work was supported by National Institutes of Health Grants AI40459 and AI51620, and by the Roche Organ Transplant Research Foundation (60495086).

² T.N. and H.A. contributed equally to this work and share principal authorship.

³ Address correspondence and reprint requests to Dr. Robert L. Fairchild, PhD, NB3-59, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195-0001. E-mail address: fairchr{at}ccf.org

⁴ Abbreviations used in this paper: AHR, acute humoral rejection; Treg, T regulatory.

This article has been cited by other articles:

				M. B. Auerbach, N. Shimoda, H. Amano, J. M. Rosenblum, D. D. Kish, J. M. Farber, and R. L. Fairchild Monokine Induced by Interferon-{gamma} (MIG/CXCL9) Is Derived from Both Donor and Recipient Sources during Rejection of Class II Major Histocompatibility Complex Disparate Skin Allografts Am. J. Pathol., June 1, 2009; 174(6): 2172 - 2181. [Abstract] [Full Text] [PDF]

				J. A Belperio and A. Ardehali Chemokines and Transplant Vasculopathy Circ. Res., August 29, 2008; 103(5): 454 - 466. [Abstract] [Full Text] [PDF]

				A. Bickerstaff, R. Pelletier, J.-J. Wang, G. Nadasdy, N. DiPaola, C. Orosz, A. Satoskar, G. Hadley, and T. Nadasdy An Experimental Model of Acute Humoral Rejection of Renal Allografts Associated with Concomitant Cellular Rejection Am. J. Pathol., August 1, 2008; 173(2): 347 - 357. [Abstract] [Full Text] [PDF]

				M. E. Wildenberg, C. G. van Helden-Meeuwsen, J. P. van de Merwe, C. Moreno, H. A. Drexhage, and M. A. Versnel Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse J. Leukoc. Biol., May 1, 2008; 83(5): 1194 - 1200. [Abstract] [Full Text] [PDF]