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- Title
T cells interact with T cells via CD40-CD154 to promote autoimmunity in type 1 diabetes.
- Authors
Baker, Rocky L.; Mallevaey, Thierry; Gapin, Laurent; Haskins, Kathryn
- Abstract
We have investigated the role of CD40 signaling in islet-reactive, diabetogenic CD4+ Th1 T-cell clones. Using multispectral flow cytometry, we showed that CD40 and CD154 are co-expressed and form complexes on the surface of activated T cells. We also demonstrate that activated Tcells can transactivate CD4+CD40+ T cells through the CD40-CD154 pathway. To investigate the role of CD40 signaling on Th1 cells, we used the diabetogenic clone BDC-5.2.9 retrovirally transduced with a truncated form of the CD40 molecule to produce a CD40 dominant-negative T-cell clone. Upon challenge with antigen in vitro, the production of IFN-γ by BDC-5.2.9 CD40DN was greatly reduced and, in vivo, the dominant-negative variant was unable to induce diabetes. Transduction with the CD40DN vector was also effective in preventing transfer of disease by primary NOD CD4+ T cells. Ex vivo analysis of pancreatic infiltrates after transfer of BDC-5.2.9 CD40DN cells revealed an overall reduction of cell numbers and cytokine production by both T cells and macrophages. These data indicate that CD40 is an important signaling molecule on autoreactive CD4+ T cells and contributes to their pathogenic effector function.
- Publication
European Journal of Immunology, 2012, Vol 42, Issue 3, p672
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201142071