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12:24
Murine Model of CD40-activation of B cells
Published on: March 5, 2010
CD40 on NOD CD4 T cells contributes to their activation and pathogenicity
Rocky L Baker1, David H Wagner, Kathryn Haskins
1Department of Immunology, University of Colorado at Denver and National Jewish Health, Denver, CO 80206, USA.
Journal of Autoimmunity
|October 28, 2008
Summary
CD40 on T cells from NOD mice is crucial for Type 1 Diabetes (T1D) development. Blocking CD40 signaling prevents T cell activation and halts diabetes transfer in mouse models.
Area of Science:
- Immunology
- Autoimmunity
- Type 1 Diabetes Research
Background:
- Type 1 Diabetes (T1D) involves autoreactive T cells attacking pancreatic beta cells.
- The role of CD40 expressed on T cells in T1D pathogenesis is not fully understood.
Purpose of the Study:
- To investigate conditions for CD40 expression on T cells from Non-Obese Diabetic (NOD) mice.
- To determine CD40's contribution to autoreactive CD4 T cell pathogenicity in T1D.
Main Methods:
- Examined CD40 expression on NOD mouse CD4 T cells upon activation via T cell receptor (TCR) and costimulation (CD28 or CD40).
- Utilized CD40-positive diabetogenic T cell clones and CD4 T cells from NOD mice.
- Conducted CD40-CD154 blocking studies.
Main Results:
- CD40 expression increased upon antigen/MHC activation and rapidly upon TCR/CD40 activation.
- CD40 costimulation enhanced T cell proliferation similarly to CD28 costimulation.
- CD40 costimulation disrupted T cell homeostasis by altering CTLA-4 expression regulation.
- Blocking CD40-CD154 interaction abrogated pathogenic T cell activation and diabetes transfer.
Conclusions:
- T cell CD40 costimulation contributes to NOD T cell pathogenicity via enhanced activation pathways.
- CD40 signaling inhibits CTLA-4 upregulation, impacting T cell regulation in T1D.
- Targeting CD40-CD154 interaction may be a therapeutic strategy for T1D.
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