Transfer of Severe Experimental Autoimmune Encephalomyelitis by IL-12- and IL-18-Potentiated T Cells Is Estrogen Sensitive

Autor: Sandhya Subramanian, Halina Offner, Jami Dwyer, Arthur A. Vandenbark, Heather Drought, Agata Matejuk, Atsushi Ito, Alex Zamora, Corwyn Hopke
Rok vydání: 2003
Předmět:
Receptors
CCR7
medicine.medical_specialty
Encephalomyelitis
Autoimmune
Experimental
Receptors
CCR4
Receptors
CCR5
T cell
Molecular Sequence Data
Immunology
Epitopes
T-Lymphocyte
C-C chemokine receptor type 7
Pregnancy Proteins
Cell Line
Myelin oligodendrocyte glycoprotein
Proinflammatory cytokine
Interferon-gamma
Mice
Adjuvants
Immunologic
T-Lymphocyte Subsets
Internal medicine
medicine
Animals
Immunology and Allergy
Secretion
Amino Acid Sequence
Glycoproteins
Drug Implants
Estradiol
biology
Tumor Necrosis Factor-alpha
Experimental autoimmune encephalomyelitis
Interleukin-18
Drug Synergism
medicine.disease
Adoptive Transfer
Interleukin-12
Peptide Fragments
Up-Regulation
Mice
Inbred C57BL
medicine.anatomical_structure
Endocrinology
Culture Media
Conditioned
Cancer research
biology.protein
Interleukin 12
Female
Myelin-Oligodendrocyte Glycoprotein
Receptors
Chemokine
Interleukin 18
Extracellular Space
Zdroj: The Journal of Immunology. 170:4802-4809
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.170.9.4802
Popis: 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 (MOG35–55). 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-α/CCR4/CCR7, and that estrogen treatment, which is known to inhibit both proinflammatory cytokines, can completely ablate this aggressive form of passive EAE.
Databáze: OpenAIRE
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