Gemcitabine directly inhibits effector CD4 T cell activation and prevents experimental autoimmune encephalomyelitis.

Pro-inflammatory T cells are critical to the pathogenesis of multiple sclerosis (MS). We investigated the potential for the anti-proliferative, pro-apoptotic drug gemcitabine to affect development of MS-relevant effector TH 1, TH 17, and Treg cells. Gemcitabine directly suppressed proliferation, activation, and induced apoptosis of all effector subsets in subtype and dose-dependent fashion. This drug also prevented development of disease in the MS model experimental autoimmune encephalomyelitis (EAE) and significantly reduced the abundance of TH 1 and TH 17 cells. Our results indicate that pathogenic CD4+ T cells may be viable targets by gemcitabine for therapeutic benefit in MS.