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

Correspondence: Professor Y Tian, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. E-mail: yptianimmu@126.com

Received 19 June 2006; Revised 1 August 2006; Accepted 1 August 2006; Published online 26 October 2006.

Abstract

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