When engineered to produce latent TGF-β1, 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-beta 1 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-beta 1 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 E4E in (SJL x BALB/c) Fl mice immunized with proteolipid protein (PLP). This protective effect was not obtained with OVA-specific TGF-beta 1 transduced Th1 cells. The transduced OVA-specific Thl cells did protect against airway hyperreactivity induced by Th2-cell mediated responses to inhaled OVA. This effect was again antigen specific and could not be obtained with untransduced OVA-specific Thl cells. In both cases these effects of antigen specific TGF-beta 1 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-beta 1 to both Thl and Th2 cell-mediated inflammatory infiltrates, (C) 2000 Elsevier Science Ltd. All rights reserved.