• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Authors

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

Journal

The Journal of experimental medicine

Publication Data

November 16, 1998

Associated Grants

None

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