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Overexpression of natural killer T cells protects Valpha14- Jalpha281 transgenic nonobese diabetic mice against diabetes.

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.

Pubmed ID: 9815260


  • Lehuen A
  • Lantz O
  • Beaudoin L
  • Laloux V
  • Carnaud C
  • Bendelac A
  • Bach JF
  • Monteiro RC


The Journal of experimental medicine

Publication Data

November 16, 1998

Associated Grants


Mesh Terms

  • Animals
  • Antigens, CD
  • Cytokines
  • Diabetes Mellitus
  • Disease Models, Animal
  • Female
  • Immunoglobulin E
  • Interleukin-4
  • Killer Cells, Natural
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell
  • Spleen
  • T-Lymphocyte Subsets
  • Th2 Cells