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 TH1, TH17, 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 TH1 and TH17 cells. Our results indicate that pathogenic CD4+ T cells may be viable targets by gemcitabine for therapeutic benefit in MS.