Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells
Copyright policy )Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells
AbstractTolerance to experimental autoimmune encephalomyelitis (EAE) in SJL mice can be induced by immunization with a mannosylated form of the proteolipid protein (M-PLP139–151), despite the presence of CFA. The state of tolerance is characterized by poor delayed-type hypersensitivity responses and the absence of clinical EAE symptoms. In vivo monitoring of CFSE-labeled PLP139–151-specific TCR-transgenic (5B6) T cells revealed that immunization with M-PLP139–151 increases the clonal expansion of 5B6 T cells that do not develop full effector functions. Moreover, nonfunctional T cells obtained from M-PLP139–151-immunized mice showed poor blastogenesis and were unable to transfer EAE to naïve recipients. Nevertheless, the in vitro production of cytokines and chemokines associated with EAE was unaffected. Importantly, tolerance induced by M-PLP139–151 was abrogated by the administration of pertussis toxin, resulting in EAE development. Our results suggest that M-PLP139–151 inhibits EAE development by affecting the differentiation of T cells into encephalitogenic effector cells.
- Delft University of Technology Netherlands
- Amsterdam UMC Netherlands
- Leiden University Medical Center Netherlands
- Leiden University Netherlands
Biomedical Research, adoptive transfer, T-Lymphocytes, Cell Count, animal cell, delayed hypersensitivity, Epitopes, Mice, allergic encephalomyelitis, cytokine, T lymphocyte, C-type lectins, Delayed-type hypersensitivity (DTH), transgenics, autoimmunity, Mus, article, female, priority journal, cytokine production, effector cell, Female, protein plp139 151, Encephalomyelitis, Autoimmune, Experimental, animal experiment, immunocompetent cell, immunization, proteolipid protein, drug tolerance, Immune Tolerance, Animals, controlled study, drug inhibition, mouse, lymphocyte transformation, Cell Proliferation, CD4+ T lymphocyte, nonhuman, pertussis toxin, chemokine, protein m plp139 151, Clone Cells, Pertussis Toxin, clonogenesis, antigen specificity, Immunization, Peptides, Tolerance, Mannose, Spleen
Biomedical Research, adoptive transfer, T-Lymphocytes, Cell Count, animal cell, delayed hypersensitivity, Epitopes, Mice, allergic encephalomyelitis, cytokine, T lymphocyte, C-type lectins, Delayed-type hypersensitivity (DTH), transgenics, autoimmunity, Mus, article, female, priority journal, cytokine production, effector cell, Female, protein plp139 151, Encephalomyelitis, Autoimmune, Experimental, animal experiment, immunocompetent cell, immunization, proteolipid protein, drug tolerance, Immune Tolerance, Animals, controlled study, drug inhibition, mouse, lymphocyte transformation, Cell Proliferation, CD4+ T lymphocyte, nonhuman, pertussis toxin, chemokine, protein m plp139 151, Clone Cells, Pertussis Toxin, clonogenesis, antigen specificity, Immunization, Peptides, Tolerance, Mannose, Spleen
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