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 organ specific autoimmunity. MHC class II restricted T-cells directed against myelin basic protein (MBP) have been shown to cause EAE in susceptible strains 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 isoform of MBP into the hematopoetic stem cells of B10.PL (73NS), SJL, and B10 mice by retrovirus-mediated gene transfer. Our experiments show expression of proviral MBP in peripheral blood and thymus following transplantation of genetically modified stem cells. Such expression does not result in deletion of MBP-specific T cells or tolerance to MBP, nor does it alter susceptibility to MBP-induced EAE in susceptible strains B10.PL and SJL. However, retrovirus-mediated gene transfer resulted in resistant B10 mice developing mild EAE. This report demonstrates that autoreactive MBP-specific T cells can be selected in the presence of endogenous antigen or an MBP-encoding retrovirus.
Peters
T R
TR
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Bodine
D M
DM
McDonagh
K T
KT
Lovett-Racke
A
A
McFarland
H F
HF
McFarlin
D E
DE
Nienhuis
A W
AW
Racke
M K
MK
D016475:3T3 Cells; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018014:Gene Transfer Techniques; D007108:Immune Tolerance; D051379:Mice; D004676:Myelin Basic Protein / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012190:Retroviridae / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
D004676:Myelin Basic Protein; D012333:RNA, Messenger