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 Google Scholar Google Scholar Articles by Ueno, A. Articles by Yang, Y. Search for Related Content PubMed PubMed Citation Articles by Ueno, A. Articles by Yang, Y.

Enhanced Early Expansion and Maturation of Semi-Invariant NK T Cells Inhibited Autoimmune Pathogenesis in Congenic Nonobese Diabetic Mice¹

Aito Ueno^2,*, Jianxiong Wang^2,*, Lu Cheng^*, Jin S. Im, Yan Shi, Steven A. Porcelli and Yang Yang^3,*

^* Julia McFarlane Diabetes Research Centre, Department of Biochemistry and Molecular Biology, and Department of Microbiology and Infectious Diseases, Faculty of Medicine, The University of Calgary, Canada; and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461

Semi-invariant NK T cell (iNKT) deficiency has long been associated with the pathogenesis of type 1 diabetes (T1D), but the linkage between this the deficiency and T1D susceptibility gene(s) remains unclear. We analyzed NOD mice subcongenic for resistant alleles of Idd9 locus in search for protective mechanisms against T1D, and found that iNKT cell development was significantly enhanced with a more advanced mature phenotype and function in mice containing Idd9.1 sublocus of B10 origin. The enhanced iNKT cell development and function suppressed effector function of diabetogenic T cells. Elimination of iNKT cells by CD1d deficiency almost abolished T1D protection in these mice. Interestingly, although the iNKT cells were responsible for a Th2 orientated cytokine profile that is often regarded as a mechanism of T1D prevention, our data suggests that the Th2 bias played little if any role for the protection. In addition, dendritic cells from the congenic NOD mice showed increased abilities to engage and potentiate iNKT cells, suggesting that a mechanism mediated by dendritic cells or other APCs may be critical for the enhanced development and maturation of iNKT cells. The products of T1D susceptibility gene(s) in Idd9.1 locus may be a key factor for this mechanism.

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 Juvenile Diabetes Research Foundation International, Canadian Diabetes Association and the Julia McFarlane Diabetes Research Center (to Y.Y.).

² A.U. and J.W. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Yang Yang, University of Calgary, Julia McFarlane Diabetes Research Center, 3330 Hospital Drive N.W., Calgary, Alberta, Canada. E-mail address: yyang{at}ucalgary.ca

⁴ Abbreviations used in this paper: iNKT cell, semi-invariant NK T cell; T1D, type 1 diabetes; DC, dendritic cell; GalCer, -galactosylceramide; SAP, SLAM-associated protein.