HLA class I antibodies provoke graft arteriosclerosis in human arteries transplanted into SCID/beige mice.

S. Galvani 1 N. Augé 1 D. Calise 1 J. C. Thiers 1 C. Canivet 1 N. Kamar 1, 2 L. Rostaing 2 M. Abbal 3 F. Sallusto 2 R. Salvayre 1 T. Böhler 1 Y. Zou 4 P. Stastny 4 A. Nègre-Salvayre 1 M. Thomsen 1, *
* Auteur correspondant
1 I2MR - Institut de médecine moléculaire de Rangueil
2 Department of Multiorgan Transplantation
3 Department of Clinical Immunology
4 University of Texas Southwestern Medical Center [Dallas]
Abstract : Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR.
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Article dans une revue
American Journal of Transplantation, Wiley, 2009, 9 (11), pp.2607-14. 〈10.1111/j.1600-6143.2009.02804.x〉
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http://www.hal.inserm.fr/inserm-00504781
Contributeur : Marie Francoise Simon <>
Soumis le : mercredi 21 juillet 2010 - 14:32:27
Dernière modification le : jeudi 13 septembre 2018 - 10:26:05

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S. Galvani, N. Augé, D. Calise, J. C. Thiers, C. Canivet, et al.. HLA class I antibodies provoke graft arteriosclerosis in human arteries transplanted into SCID/beige mice.. American Journal of Transplantation, Wiley, 2009, 9 (11), pp.2607-14. 〈10.1111/j.1600-6143.2009.02804.x〉. 〈inserm-00504781〉

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