Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis

Tamara Saksida, Djordje Miljkovic, Gordana Timotijevic, Ivana Stojanovic, Sanja Mijatovic, Paolo Fagone, Katia Mangano, Santa Mammana, Claudio Farina, Ester Ascione, Valentina Maiello, Ferdinando Nicoletti, Stanislava Stosic-Grujicic

Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1β, TNF, IFN-γ, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3+ T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NFκB signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis.