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

Gene Therapy volume 14, pages 383–395 (2007)Cite this article

Abstract

The aim of this study was to investigate the immunomodulatory effects and mechanism of action of alpha-melanocyte-stimulating hormone (α-MSH) gene modified proteolipid protein (PLP) 139–151-specific T cells (TPLP-α-MSH) in the SJL mouse model of experimental autoimmune encephalomyelitis (EAE). PLP139-151-specific T cells (TPLP cells) were transduced with a recombinant adeno-associated virus 2 (rAAV2) encoding α-MSH. After activation with PLP139-151 in vitro, TPLP-α-MSH cells secreted high levels of α-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 TPLP-α-MSH cells could suppress the induction of adoptive transfer EAE. More importantly, our studies demonstrated that TPLP-α-MSH cells had preventive and therapeutic effect on active relapse-remitting EAE (REAE) in an antigen-inducible manner. Suppression of REAE by TPLP-α-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 α-MSH by rAAV2-mediated α-MSH-transduced PLP139-151-specific T cells (TPLP-α-MSH) would be a desirable new approach to the treatment of autoimmune disease in the CNS.

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Abbreviations

AAV:

adeno-associated virus

CNS:

central nervous system

EAE:

experimental autoimmune encephalomyelitis

hrGFP:

green fluorescent protein

MS:

multiple sclerosis

α-MSH:

α-melanocyte-stimulating hormone

PLP:

proteolipid protein

REAE:

relapsing-remitting EAE

v.g.:

vector genomes

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (30271210). We thank Dr Xuetao Cao and Yizhi Yu for their helpful suggestions. We are also grateful for the skillful animal care of Liyun Shi.

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Authors and Affiliations

  1. Institute of Immunology, Second Military Medical University, Shanghai, People's Republic of China

    D Han, Y Tian, M Zhang, Z Zhou & J Lu

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  1. D Han
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Correspondence to Y Tian.

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Han, D., Tian, Y., Zhang, M. et al. Prevention and treatment of experimental autoimmune encephalomyelitis with recombinant adeno-associated virus-mediated α-melanocyte-stimulating hormone-transduced PLP139-151-specific T cells. Gene Ther 14, 383–395 (2007). https://doi.org/10.1038/sj.gt.3302862

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