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Javad Rasouli, Bogoljub Ciric, Jaime Imitola, Patricia Gonnella, Daniel Hwang, Kedar Mahajan, Elisabeth R Mari, Farinaz Safavi, Thomas P Leist, Guang-Xian Zhang, Abdolmohamad Rostami, Expression of GM-CSF in T Cells Is Increased in Multiple Sclerosis and Suppressed by IFN-β Therapy, The Journal of Immunology, Volume 194, Issue 11, June 2015, Pages 5085–5093, https://doi.org/10.4049/jimmunol.1403243
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Abstract
Multiple sclerosis (MS) is an autoimmune disease of the CNS. Studies in animal models of MS have shown that GM-CSF produced by T cells is necessary for the development of autoimmune CNS inflammation. This suggests that GM-CSF may have a pathogenic role in MS as well, and a clinical trial testing its blockade is ongoing. However, there have been few reports on GM-CSF production by T cells in MS. The objective of this study was to characterize GM-CSF production by T cells of MS patients and to determine the effect of IFN-β therapy on its production. GM-CSF production by peripheral blood (PB) T cells and the effects of IFN-β were characterized in samples of untreated and IFN-β–treated MS patients versus healthy subjects. GM-CSF production by T cells in MS brain lesions was analyzed by immunofluorescence. Untreated MS patients had significantly greater numbers of GM-CSF+CD4+ and CD8+ T cells in PB compared with healthy controls and IFN-β–treated MS patients. IFN-β significantly suppressed GM-CSF production by T cells in vitro. A number of CD4+ and CD8+ T cells in MS brain lesions expressed GM-CSF. Elevated GM-CSF production by PB T cells in MS is indicative of aberrant hyperactivation of the immune system. Given its essential role in animal models, abundant GM-CSF production at the sites of CNS inflammation suggests that GM-CSF contributes to MS pathogenesis. Our findings also reveal a potential mechanism of IFN-β therapy, namely suppression of GM-CSF production.
