TGF-beta 1 null mutation leads to CD154 upregulated expression in affectedtissues

The TGF-beta1(-/-) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that lea ds to multifocal tissue inflammation and autoantibody production in TGF-bet a1(-/-) mice. Heart, lung, liver, and salivary gland from TGF-beta1(-/-) we re assessed for CD154 expression by RT-PCR and immunohistochemistry. Compar ed to wild-type littermates, CD154 expression was elevated in all tissues s tudied. Furthermore, IL-12 mRNA was expressed in the salivary gland and hea rt of TGF-beta1(-/-) mice and not in wildtype littermates. This suggests th at the CD154 pathway is activated in these tissues. This shows that TGF-bet a1 regulates CD154 expression leading to spontaneous IL-12 production and a utoimmunity.