Adoptive cellular gene therapy of autoimmune disease.
Autoimmune disorders represent inappropriate immune responses directed at self-tissue. Because CD4+ T cells are important mediators in the pathogenesis of autoimmune disease, they are ideal candidates for cell-based gene therapy. Using retrovirally-transduced cells and luciferase bioluminescence, we have demonstrated that primary T cells and hybridomas, rapidly and preferentially home to the sites of inflammation in organ-specific autoimmune disease. These cells, transduced with retroviral vectors to drive expression of various 'regulatory proteins', such as IL-4, IL-10 and IL-12p40, deliver these immunoregulatory proteins to the inflamed lesions, providing therapy for experimental models of autoimmune disease such as EAE, CIA and NOD mice. This technique was originally developed in our lab in the murine model of multiple sclerosis, EAE, where T cell hybridomas reactive with myelin basic protein (MBP) were transduced to express and used to deliver the modulatory cytokine, IL-4. Recently we have observed that the cytokine receptor antagonist, IL-12p40 transduced anti-myelin basic protein (MBP) TCR-transgenic T cells (but not CII-reactive T cells) were effective in preventing EAE whereas the CII-reactive, but not MBP-reactive T cells, transduced to express IL-12p40, would treat CIA.
Slavin
Anthony J
AJ
Stanford University School of Medicine, Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford University Medical Center, 300 Pasteur Dve, CCSR 2225, Stanford, CA 94305, USA.
Tarner
Ingo H
IH
Nakajima
Atsuo
A
Urbanek-Ruiz
Irene
I
McBride
Jacqueline
J
Contag
Christopher H
CH
Fathman
C Garrison
CG
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008163:Luminescent Measurements; D051379:Mice; D012190:Retroviridae / Q000235:genetics