Prevention and treatment of experimental autoimmune encephalomyelitis with recombinant adeno-associated virus-mediated alpha-melanocyte-stimulating hormone-transduced PLP139-151-specific T cells.
The aim of this study was to investigate the immunomodulatory effects and mechanism of action of alpha-melanocyte-stimulating hormone (alpha-MSH) gene modified proteolipid protein (PLP) 139-151-specific T cells (T(PLP-alpha-MSH)) in the SJL mouse model of experimental autoimmune encephalomyelitis (EAE). PLP139-151-specific T cells (T(PLP) cells) were transduced with a recombinant adeno-associated virus 2 (rAAV2) encoding alpha-MSH. After activation with PLP139-151 in vitro, T(PLP-alpha-MSH) cells secreted high levels of alpha-MSH and also demonstrated an altered Th1-like cytokine pattern as well as a high frequency of CD4(+)CD25(+)Treg cells. Transfer studies showed that T(PLP-alpha-MSH) cells could suppress the induction of adoptive transfer EAE. More importantly, our studies demonstrated that T(PLP-alpha-MSH) cells had preventive and therapeutic effect on active relapse-remitting EAE (REAE) in an antigen-inducible manner. Suppression of REAE by T(PLP-alpha-MSH) cells was associated with a general reduction of inflammatory central nervous system (CNS) infiltrates, a pronounced decrease in Th1 cytokines and chemokines expression and an increase in Th2 cytokines. These data strongly suggested that local delivery of alpha-MSH by rAAV2-mediated alpha-MSH-transduced PLP139-151-specific T cells (T(PLP-alpha-MSH)) would be a desirable new approach to the treatment of autoimmune disease in the CNS.
Han
D
D
Institute of Immunology, Second Military Medical University, Shanghai, People's Republic of China. yptianimmu@126.com
Tian
Y
Y
Zhang
M
M
Zhou
Z
Z
Lu
J
J
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D000229:Dependovirus / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D018991:Myelin Proteolipid Protein / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism / Q000637:transplantation*; D018418:Th2 Cells / Q000276:immunology; D014161:Transduction, Genetic / Q000379:methods; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D000521:alpha-MSH