Th2 T cells expressing transgene PDGF-A serve as vectors for gene therapy in autoimmune demyelinating disease.
We hypothesized that T cells can be genetically modified to express growth factor transgene products capable of inducing oligodendrocyte progenitor proliferation. Autoreactive T cells isolated from SWXJ mice immunized with the p139-151 determinant of myelin proteolipid protein (PLP) were transfected with an antigen-inducible transgene for platelet-derived growth factor-A (PDGF), a growth factor important in regulating the development of oligodendrocytes. Isolated antigen-specific T cell clones expressed the PDGF transgene when stimulated with PLP 139-151 peptide and produced biologically active PDGF capable of inducing proliferation of oligodendrocyte progenitor cells. Furthermore, upon adoptive transfer, the PDGF transfected T cells migrated to the CNS and ameliorated ongoing disease. Our data indicate that autoreactive memory Th2 cells can be genetically modified so that upon engagement with self antigen they produce regenerative growth factors capable of mediating tissue repair during autoimmune disease.
Mathisen
P M
PM
Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Yu
M
M
Yin
L
L
Johnson
J M
JM
Kawczak
J A
JA
Nishiyama
A
A
Tuohy
V K
VK
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens; D001483:Base Sequence; D002454:Cell Differentiation; D002465:Cell Movement; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D051379:Mice; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013234:Stem Cells / Q000473:pathology / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology; D014162:Transfection
D001324:Autoantigens; D017931:DNA Primers; D018076:DNA, Complementary; D018991:Myelin Proteolipid Protein; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A