CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes

Immunity. 1996 Sep;5(3):285-93. doi: 10.1016/s1074-7613(00)80323-4.


CD28 ligation delivers a costimulatory signal important in T cell activation. This study demonstrates that the disruption of the CD28/B7 pathway early in the nonobese diabetic mouse strain, using CD28-/- and CTLA41g transgenic mice, promoted the development and progression of spontaneous autoimmune diabetes. Functional analyses of T cells isolated from CD28-deficient mice demonstrated that the GAD-specific T cells produced enhanced Th1-type cytokines (IL-2 and IFN gamma) and diminished Th2-type cytokine, IL-4. Moreover, there was a significant decrease in serum levels of anti-GAD antibodies of the IgG1 isotype consistent with a profound suppression of Th2-type responses in these animals. Thus, the early differentiation of naive diabetogenic T cells into the Th2 subset is dependent upon CD28 signaling and extends our understanding of the importance of Th1/Th2 balance in the regulation of this spontaneous autoimmune disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / physiology
  • Autoantigens / immunology
  • B7-1 Antigen / physiology*
  • Base Sequence
  • CD28 Antigens / physiology*
  • CTLA-4 Antigen
  • Diabetes Mellitus, Type 1 / immunology*
  • Glutamate Decarboxylase / immunology
  • Immunoconjugates*
  • Immunoglobulin G / classification
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Molecular Sequence Data
  • Ovalbumin / immunology
  • Th1 Cells / physiology*
  • Th2 Cells / physiology*


  • Antigens, CD
  • Antigens, Differentiation
  • Autoantigens
  • B7-1 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Immunoglobulin G
  • Abatacept
  • Ovalbumin
  • Glutamate Decarboxylase