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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900200v1 183/3/1560    most recent 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 Google Scholar Articles by Gorczynski, R. M. Articles by Boudakov, I. PubMed PubMed Citation Articles by Gorczynski, R. M. Articles by Boudakov, I.

Expression of a CD200 Transgene Is Necessary for Induction but Not Maintenance of Tolerance to Cardiac and Skin Allografts¹

Reginald M. Gorczynski^2,*,, Zhiqi Chen^*, William He^*, Ismat Khatri^*, Yang Sun^*, Kai Yu^* and Ivo Boudakov^*

^* The Toronto Hospital, University Health Network, Toronto, Ontario, Canada; and Departments of Surgery and Immunology, University of Toronto, Toronto, Ontario, Canada

CD200, a type 2 transmembrane molecule of the Ig supergene family, can induce immunosuppression in a number of biological systems, as well as promote increased graft acceptance, following binding to its receptors (CD200Rs). Skin and cardiac allograft acceptance are readily induced in transgenic mice overexpressing CD200 under control of a doxycycline-inducible promoter, both of which are associated with increased intragraft expression of mRNAs for a number of genes associated with altered T cell subset differentiation, including GATA-3, type 2 cytokines (IL-4, IL-13), GITR, and Foxp3. Interestingly, some 12–15 days after grafting, induction of transgenic CD200 expression can be stopped (by doxycycline withdrawal), without obvious significant effect on graft survival. However, neutralization of all CD200 expression (including endogenous CD200 expression) by anti-CD200 mAb caused graft loss, as did introduction of an acute inflammatory stimulus (LPS, 10 µg/mouse, delivered by i.p. injection). We conclude that even with apparently stably accepted tissue allografts, disruption of the immunoregulatory balance by an intense inflammatory stimulus can cause graft loss.

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 a grant from the Heart and Stroke Foundation.

² Address correspondence and reprint requests to: Dr. Reginald M. Gorczynski, The Toronto Hospital, University Health Network, 2-805, MaRS Tower, 101 College Street, Toronto, Ontario M5G 1L7, Canada. E-mail address: rgorczynski{at}uhnres.utoronto.ca

³ Abbreviations used in this paper: DC, dendritic cell; Dox, doxycycline; MLC, mixed leukocyte culture; PD-1, programmed cell death-1; Treg, regulatory T cell.