T cells interact with T cells via CD40-CD154 to promote autoimmunity in type 1 diabetes.
Eur J Immunol
; 42(3): 672-80, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22488364
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoimunidade
/
Antígenos CD40
/
Ligante de CD40
/
Diabetes Mellitus Tipo 2
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article