Expression of GM-CSF in T Cells Is Increased in Multiple Sclerosis and Suppressed by IFN-β Therapy.
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.
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Javad
J
Rasouli
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Bogoljub
B
Ciric
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Jaime
J
Imitola
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Patricia
P
Gonnella
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Daniel
D
Hwang
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Kedar
K
Mahajan
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Elisabeth R
ER
Mari
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Farinaz
F
Safavi
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Thomas P
TP
Leist
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Guang-Xian
GX
Zhang
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107 Rostami@jefferson.edu.
Abdolmohamad
A
Rostami
D000328:Adult; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016899:Interferon-beta / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology
D016899:Interferon-beta; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor