TY - JOUR
T1 - Transfer of severe experimental autoimmune encephalomyelitis by IL-12- and IL-18-potentiated T cells is estrogen sensitive
AU - Ito, Atsushi
AU - Matejuk, Agata
AU - Hopke, Corwyn
AU - Drought, Heather
AU - Dwyer, Jami
AU - Zamora, Alex
AU - Subramanian, Sandhya
AU - Vandenbark, Arthur A.
AU - Offner, Halina
PY - 2003/5/1
Y1 - 2003/5/1
N2 - The aim of this study was to evaluate the roles of IL-18 and IL-12 in potentiating the encephalitogenic activity of T cell lines specific for myelin oligodendrocyte glycoprotein (MOG35-5). MOG-specific T cells stimulated with anti-CD3 and anti-CD28 in the presence of IL-12 or IL-18 alone transferred only mild experimental autoimmune encephalomyelitis (EAE) into a low percentage of recipients. However, T cells cocultured with both cytokines transferred aggressive clinical and histological EAE into all recipients. Coculture of T cells with IL-12 enhanced the secretion of IFN-γ but not TNF-α, whereas coculture with IL-18 enhanced the secretion of TNF-α, but not INF-γ. However, coculture with both IL-18 and IL-12 induced high levels of both TNF-α and IFN-γ. Additionally, IL-12 selectively enhanced mRNA expression of CCR5, whereas IL-18 selectively enhanced the expression of CCR4 and CCR7, and CCR4 and CCR5 were coexpressed on the surface of T cells cocultured with IL-12 and IL-18. Finally, estrogen treatment, previously found to inhibit both TNF-α and IFN-γ production, completely abrogated all signs of passive EAE. These data demonstrate that optimal potentiation of encephalitogenic activity can be achieved by conditioning MOG-specific T cells with the combination of IL-12 and IL-18, which, respectively, induce the secretion of IFN-γ/CCR5 and TNF-γ/CCR4/CCR7, and that estrogen treatment, which is known to inhibit both proinflammatory cytokines, can completely ablate this aggressive form of passive EAE.
AB - The aim of this study was to evaluate the roles of IL-18 and IL-12 in potentiating the encephalitogenic activity of T cell lines specific for myelin oligodendrocyte glycoprotein (MOG35-5). MOG-specific T cells stimulated with anti-CD3 and anti-CD28 in the presence of IL-12 or IL-18 alone transferred only mild experimental autoimmune encephalomyelitis (EAE) into a low percentage of recipients. However, T cells cocultured with both cytokines transferred aggressive clinical and histological EAE into all recipients. Coculture of T cells with IL-12 enhanced the secretion of IFN-γ but not TNF-α, whereas coculture with IL-18 enhanced the secretion of TNF-α, but not INF-γ. However, coculture with both IL-18 and IL-12 induced high levels of both TNF-α and IFN-γ. Additionally, IL-12 selectively enhanced mRNA expression of CCR5, whereas IL-18 selectively enhanced the expression of CCR4 and CCR7, and CCR4 and CCR5 were coexpressed on the surface of T cells cocultured with IL-12 and IL-18. Finally, estrogen treatment, previously found to inhibit both TNF-α and IFN-γ production, completely abrogated all signs of passive EAE. These data demonstrate that optimal potentiation of encephalitogenic activity can be achieved by conditioning MOG-specific T cells with the combination of IL-12 and IL-18, which, respectively, induce the secretion of IFN-γ/CCR5 and TNF-γ/CCR4/CCR7, and that estrogen treatment, which is known to inhibit both proinflammatory cytokines, can completely ablate this aggressive form of passive EAE.
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U2 - 10.4049/jimmunol.170.9.4802
DO - 10.4049/jimmunol.170.9.4802
M3 - Article
C2 - 12707362
AN - SCOPUS:0242416985
SN - 0022-1767
VL - 170
SP - 4802
EP - 4809
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -