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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
Published on: May 6, 2013
Breakpoints in immunoregulation required for Th1 cells to induce diabetes
Margaret Neighbors1, Suzanne B Hartley, Xiuling Xu
1MAXYGEN, Redwood City, USA.
European Journal of Immunology
|August 26, 2006
Summary
Regulatory pathways like CTLA-4 signaling can prevent autoimmune diabetes by inhibiting autoreactive T cells. Blocking CTLA-4 in Th1 cells can lead to insulitis and diabetes development, highlighting its role in maintaining tolerance.
Area of Science:
- Immunology
- Autoimmunity
- T cell biology
Background:
- A novel TCR-transgenic mouse line (TCR7) was developed with CD4+ T cells specific for a hen egg lysozyme (HEL) epitope.
- These autoreactive T cells showed increased frequency in lymphoid organs compared to controls.
Purpose of the Study:
- To investigate the development of autoimmune diabetes from autoreactive T cells.
- To understand the role of T cell polarization and regulatory pathways in autoimmunity.
Main Methods:
- Adoptive transfer of TCR7 T cells into RIP-HEL transgenic mice.
- Polarization of TCR7 T cells into Th1 or Th2 phenotypes prior to transfer.
- Manipulation of CTLA-4 signaling during adoptive transfer experiments.
Main Results:
- TCR7 T cells expanded in recipients with high serum HEL but did not initially infiltrate islets.
- Prior polarization to Th1 or Th2 induced insulitis (islet infiltration).
- Progression to autoimmune diabetes occurred only with Th1-polarized cells and simultaneous CTLA-4 signaling blockade.
Conclusions:
- CTLA-4 signaling is crucial for suppressing differentiated autoreactive effector Th1 cells.
- Regulatory pathways can prevent the transition from tolerance to autoimmune diabetes.
- This study elucidates mechanisms controlling autoimmune diabetes development.
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