Targeting myelin proteolipid protein to the MHC class I pathway by ubiquitination modulates the course of experimental autoimmune encephalomyelitis.
Relapsing-remitting experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model, is induced in mice by injection of myelin proteolipid protein (PLP) encephalitogenic peptide, PLP139-151, in adjuvant. In this study, prior to EAE induction, mice were vaccinated with a bacterial plasmid encoding a PLP-ubiquitin fusion (pCMVUPLP). During the relapse phase of EAE, clinical signs, histopathologic changes, in vitro lymphoproliferation to PLP139-151 and interferon-gamma levels were reduced in pCMVUPLP-vaccinated mice, compared to mock-vaccinated mice (controls). Lymphocytes from pCMVUPLP-vaccinated mice produced interleukin-4, a cytokine lacking in controls. Thus, pCMVUPLP vaccination can modulate the relapse after EAE induction.
Theil
Diethilde J
DJ
Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, RM 3R330, Salt Lake City, Utah 84132, United States.
Libbey
Jane E
JE
Rodriguez
Fernando
F
Whitton
J Lindsay
JL
Tsunoda
Ikuo
I
Derfuss
Tobias J
TJ
Fujinami
Robert S
RS
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D054875:Ubiquitination / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151)