Prevention and treatment of experimental autoimmune encephalomyelitis with recombinant adeno-associated virus-mediated alpha-melanocyte-stimulating hormone-transduced PLP139-151-specific T cells.

Full Abstract

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.

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Author information

Author/s: Han, D (D); Tian, Y (Y); Zhang, M (M); Zhou, Z (Z); Lu, J (J);

Affiliation: Institute of Immunology, Second Military Medical University, Shanghai, People's Republic of China. yptianimmu(-atsign-)126.com

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Gene therapy (Gene Ther), published in England. (Language: eng)

Reference: 2007-Mar; vol 14 (issue 5) : pp 383-95

Dates: Created 2007/02/20; Completed 2007/06/29;

PMID: 17066098, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adoptive Transfer - methods
Animals
Central Nervous System - immunology; pathology
Cytokines - immunology
Dependovirus - genetics
Encephalomyelitis, Autoimmune, Experimental - immunology; prevention & control; therapy
Flow Cytometry
Gene Therapy - methods
Genetic Vectors - administration & dosage; genetics
Lymphocyte Activation

Lymphocyte Activation
Mice
Mice, Mutant Strains
Myelin Proteolipid Protein - metabolism
Peptide Fragments - metabolism
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes - metabolism; secretion; transplantation
Th2 Cells - immunology
Transduction, Genetic - methods
alpha-MSH - genetics; metabolism; secretion

Associated Chemicals: Cytokines (0) ; Myelin Proteolipid Protein (0) ; Peptide Fragments (0) ; proteolipid protein 139-151 (0) ; alpha-MSH (581-05-5)

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