When engineered to produce latent TGF-beta1, antigen specific T cells down regulate Th1 cell-mediated autoimmune and Th2 cell-mediated allergic inflammatory processes.
To determine whether T cells which produce large amounts of latent TGF-beta1 are capable of down-regulating autoimmune and allergic disease, myelin basic protein (MBP)-specific and ovalbumin (OVA)-specific BALB/c cloned Th1 cells were transduced with cDNA for murine TGF-beta1 by coculture with fibroblasts producing a genetically engineered retrovirus. The transduced MBP-specific Th1 cells were found to lose the capacity to provoke EAE in BALB/c mice, and to gain instead the ability to protect against EAE in (SJLxBALB/c) F1 mice immunized with proteolipid protein (PLP). This protective effect was not obtained with OVA-specific TGF-beta1 transduced Th1 cells. The transduced OVA-specific Th1 cells did protect against airway hyperreactivity induced by Th2-cell mediated responses to inhaled OVA. This effect was again antigen specific and it also could not be obtained with untransduced OVA-specific Th1 cells. In both cases these effects of antigen specific TGF-beta1 transduced T cells were nullified by administration of neutralizing anti-TGF-beta mAb. Thus, the antigen specificity of the cloned T cells allows the site-specific local delivery of therapeutic active TGF-beta1 to both Th1 and Th2 cell-mediated inflammatory infiltrates.
Thorbecke
G J
GJ
Department of Pathology, NYU School of Medicine, New York, NY 10016, USA. thorbj01@mcrcr.med.nyu.edu
Umetsu
D T
DT
deKruyff
R H
RH
Hansen
G
G
Chen
L Z
LZ
Hochwald
G M
GM
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism; D015551:Autoimmunity / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D004676:Myelin Basic Protein; D016212:Transforming Growth Factor beta