A novel retroviral gene therapy approach to inhibit specific antibody production and suppress experimental autoimmune encephalomyelitis induced by MOG and MBP.
Experimental autoimmune encephalomyelitis (EAE), an inflammatory, demyelinating disease of the central nervous system, serves as a system for testing potential therapeutic approaches for human multiple sclerosis (MS). Our group has previously shown that peripheral tolerance of both T(H)1 and T(H)2 compartments can be induced using retrovirally transduced B cells that express myelin basic protein (MBP). With this treatment, passive transfer of clinical EAE can be blocked. Herein, we demonstrate that inhibition of antibody production specific for myelin oligodendrocyte glycoprotein (MOG) and suppression of chronic EAE induced by MOG in susceptible mice can be elicited by MOG-Ig gene therapy. Moreover, using a full-length MBP construct, we observed a delayed disease onset and/or decreased severity in Ac1-11 induced EAE. This suggests the possibility of tailoring immune response without knowing the specific epitope per se. Of special interest is that we are able to detect the transduced B cells not only in the spleen but also in the CNS. Our results indicate that utilizing retrovirally transduced B cells as vehicle may be a feasible approach for tolerance induction in patients with MS.
Xu
Biying
B
American Red Cross, Holland Lab for the Biomedical Sciences, Rockville, MD 20855, USA.
Scott
David W
DW
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007108:Immune Tolerance; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D012190:Retroviridae / Q000276:immunology; D014161:Transduction, Genetic
C571326:MOG protein, human; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein