Stem cells ameliorate EAE via an indoleamine 2,3-dioxygenase (IDO) mechanism

Syngeneic, pluripotent Lin−Sca1+ bone marrow stem cells (SC), transferred to mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis, enhanced recovery, prevented relapses and promoted myelin repair. SC-treated mice showed elevated interferon-γ production and induction of indoleamine 2,3-dioxygenase (IDO) in CD11c+ dendritic cells (DC). IDO induction was specific since in the presence of IDO-producing CD11c+ DC, PLP stimulated T cell proliferation was inhibited and the IDO-inhibitor, 1-MT, abrogated the SC effect. Relapse prevention during chronic disease correlated with decreased responsiveness to PLP178–191 and MBP85–99. Thus, pluripotent SC induce IDO in DC leading to inhibition of antigen reactivity and spreading in EAE.