Retrovirus mediated gene transfer of the self antigen MBP into the bone marrow of mice alters resistance to experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a prototypic model of or gan specific autoimmunity. MHC class II restricted T-cells directed against myelin basic protein (MBP) have been shown to cause EAE in susceptible str ains of mice. We have asked whether the introduction of a gene encoding an autoantigen (MBP) into the hematopoetic stem cells of mice would result in tolerance to that protein. We have introduced cDNA encoding the 21.5 kDa is oform of MBP into the hematopoetic stem cells of B10.PL (73NS), SJL, and B1 0 mice by retrovirus-mediated gene transfer. Our experiments show expressio n of proviral MBP in peripheral blood and thymus following transplantation of genetically modified stem cells. Such expression does not result in dele tion of MBP-specific T cells or tolerance to MBP, nor does it alter suscept ibility to MBP-induced EAE in susceptible strains B10.PL and Sn. However, r etrovirus-mediated gene transfer resulted in resistant B10 mice developing mild EAE. This report demonstrates that autoreactive MBP-specific T cells c an be selected in the presence of endogenous antigen or an MBP-encoding ret rovirus, (C) 2000 Elsevier Science B.V. All rights reserved.