Expression of GM-CSF in T Cells Is Increased in Multiple Sclerosis and Suppressed by IFN-β Therapy

• Published in: The Journal of immunology (1950) Vol. 194; no. 11; pp. 5085 - 5093
• Main Authors: Rasouli, Javad, Ciric, Bogoljub, Imitola, Jaime, Gonnella, Patricia, Hwang, Daniel, Mahajan, Kedar, Mari, Elisabeth R, Safavi, Farinaz, Leist, Thomas P, Zhang, Guang-Xian, Rostami, Abdolmohamad
• Format: Journal Article
• Language: English
• Published: United States 01.06.2015
• Subjects: Adult; Brain - cytology; Brain - immunology; Brain - pathology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Female; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Humans; Inflammation - immunology; Interferon-beta - therapeutic use; Interferon-gamma - biosynthesis; Lymphocyte Activation - immunology; Male; Middle Aged; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1403243

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.