Treatment of experimental autoimmune encephalomyelitis with genetically modified memory T cells.
The migratory properties of memory T cells provide a model vector system for site-specific delivery of therapeutic transgene factors to autoimmune inflammatory lesions. Lymph node cells from (SWRxSJL)F1 mice immunized with the p139-151 determinant of myelin proteolipid protein (PLP) were transfected with a DNA construct that placed the anti-inflammatory cytokine interleukin-10 (IL-10) cDNA under control of an antigen-inducible IL-2 promoter region. Isolated T cell clones demonstrated antigen-inducible expression of transgene IL-10 and expressed cell surface markers consistent with the phenotype of normal memory T cells. Upon adoptive transfer, transfected T cell clones were able to inhibit onset of experimental autoimmune encephalomyelitis (EAE) and to treat EAE animals therapeutically after onset of neurologic signs. Semiquantitative immunocytochemistry showed a significant correlation between decreased demyelination and treatment with the transfected T cells. Taken together, these data indicate the autoreactive T cells can be genetically designed to produce therapeutic factors in an antigen-inducible manner resulting in a decreased severity of clinical and histological autoimmune demyelinating disease.
Mathisen
P M
PM
The Cleveland Clinic Foundation, Research Institute, Department of Immunology, FFb-1, Cleveland, Ohio 44195, USA.
Yu
M
M
Johnson
J M
JM
Drazba
J A
JA
Tuohy
V K
VK
D000818:Animals; D004247:DNA / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007156:Immunologic Memory / Q000235:genetics; D016219:Immunotherapy, Adoptive; D016753:Interleukin-10 / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*
D016753:Interleukin-10; D004247:DNA