GM-CSF promotes chronic disability in EAE by altering the composition of CNS myeloid cells, but is dispensable for disease induction

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been portrayed as a critical cytokine in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and, ostensibly, in multiple sclerosis. C57BL/6 mice deficient in GM-CSF are resistant to EAE induced by immunization with the 35–55 fragment of myelin oligodendrocyte glycoprotein (MOG 35–55 ). The mechanism of action of GM-CSF in EAE is poorly understood. Here we show that GM-CSF augments the accumulation of MOG 35–55 -specific T cells in the skin draining lymph nodes of primed mice, but is not required for the development of encephalitogenic T cells. Abrogation of GM-CSF receptor signaling in adoptive transfer recipients of MOG 35–55 -specific T cells did not alter the incidence of EAE, or the trajectory of its initial clinical course, but limited the extent of chronic CNS tissue damage and neurological disability. The attenuated clinical course was associated with a relative dearth of MOG 35–55 -specific T cells, myeloid dendritic cells, and neutrophils, and an abundance of B cells, within CNS infiltrates. Our data indicate that GM-CSF drives chronic tissue damage and disability in EAE via pleiotropic pathways, but is dispensable during early lesion formation and the onset of neurological deficits.