Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice

IL-10-secreting regulatory T cell lines specific to glatiramer acetate [poly(Y,E,A,K)n] or poly(Y,F,A,K)n have been established from the enlarged spleen and lymph nodes that result from copolymer treatment of SJL mice in which experimental autoimmune encephalomyelitis was induced by PLP139-151. Thes...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-04, Vol.105 (13), p.5172-5176
Main Authors: Stern, Joel N.H, Keskin, Derin B, Zhang, Hong, Lv, HuiJuan, Kato, Zenichiro, Strominger, Jack L
Format: Article
Language:English
Subjects:
Adoptive Transfer
Amino acids
Amino Acids - immunology
Animals
Autoimmune diseases
Biological Sciences
Bystander Effect
Cattle
Cell Line
Cell lines
Cell Proliferation
Cell Separation
Copolymers
Cytokines
Encephalomyelitis, Autoimmune, Experimental - chemically induced
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - metabolism
Forkhead Transcription Factors - metabolism
Immunization
Interleukin-10 - metabolism
Interleukins
Mice
Neurons
Peptides - immunology
Phenotype
Receptors, Antigen, T-Cell - immunology
Rodents
T cell receptors
T lymphocytes
T-Lymphocytes, Regulatory - cytology
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
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Summary:IL-10-secreting regulatory T cell lines specific to glatiramer acetate [poly(Y,E,A,K)n] or poly(Y,F,A,K)n have been established from the enlarged spleen and lymph nodes that result from copolymer treatment of SJL mice in which experimental autoimmune encephalomyelitis was induced by PLP139-151. These CD4+CD25+T cell lines secrete high levels of IL-10 and IL-13 but only small amounts of IL-4 and virtually no TGF-β, IL-17, IL-6, IFN-γ, or TNF-α. Their phenotypes are particularly characterized by the absence of Foxp3 and the presence of two TNFR family members, CD30 and GITR. The lines proliferated specifically to the immunizing copolymers but were autoantigen-nonspecific, in that the same T cell line could suppress autoimmunity induced by three different autoantigens in SJL mice, i.e., PLP139-151(EAE), MBP85-99 (EAE), and bovine peripheral nerve myelin (experimental autoimmune neuritis), indicating they function by bystander suppression.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0712131105