Overexpression of Natural Killer T Cells Protects Vα14-Jα281 Transgenic Nonobese Diabetic Mice against Diabetes

作者：Agnès Lehuen, Olivier J Lantz, Lucie Beaudoin, Véronique Laloux, Claude Carnaud, Albert S Bendelac, Jean‐François Bach, Renato C. Monteiro · 发表于：The Journal of Experimental Medicine · 年份：1998 · DOI：10.1084/jem.188.10.1831 · 被引用次数：392 · 研究领域：Immune Cell Function and Interaction、Diabetes and associated disorders、T-cell and B-cell Immunology

Progression to destructive insulitis in nonobese diabetic (NOD) mice is linked to the failure of regulatory cells, possibly involving T helper type 2 (Th2) cells. Natural killer (NK) T cells might be involved in diabetes, given their deficiency in NOD mice and the prevention of diabetes by adoptive transfer of alpha/beta double-negative thymocytes. Here, we evaluated the role of NK T cells in diabetes by using transgenic NOD mice expressing the T cell antigen receptor (TCR) alpha chain Valpha14-Jalpha281 characteristic of NK T cells. Precise identification of NK1.1(+) T cells was based on out-cross with congenic NK1.1 NOD mice. All six transgenic lines showed, to various degrees, elevated numbers of NK1.1(+) T cells, enhanced production of interleukin (IL)-4, and increased levels of serum immunoglobulin E. Only the transgenic lines with the largest numbers of NK T cells and the most vigorous burst of IL-4 production were protected from diabetes. Transfer and cotransfer experiments with transgenic splenocytes demonstrated that Valpha14-Jalpha281 transgenic NOD mice, although protected from overt diabetes, developed a diabetogenic T cell repertoire, and that NK T cells actively inhibited the pathogenic action of T cells. These results indicate that the number of NK T cells strongly influences the development of diabetes.