Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta1

A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was transduced with cDNA for murine latent transforming growth factor-[Beta]1 (TGF-[Beta]1) by coculture with fibroblasts producing a genetically engineered retrovirus. When SJL x BALB/c F1 mice, immunized 12-15 days earlier with proteolipid protein in complete Freund's adjuvant, were injected with 3 x [10.sup.6] cells from MBP-activated untransduced cloned Th1 cells, the severity of experimental allergic encephaiomyelitis (EAE) was slightly increased. In contrast, MBP-activated (but not resting) latent TGF-[Beta]1-transduced T cells significantly delayed and ameliorated EAE development. This protective effect was negated by simultaneously injected anti.TGF-[Beta]1. The transduced cells secreted 2-4 ng/ml of latent TGF-[Beta]1 into their culture medium, whereas control cells secreted barely detectable amounts. mRNA profiles for tumor necrosis factor, lymphotoxin, and interferon-[Gamma] were similar before and after transduction; interleukin-4 and -10 were absent. TGF-[Beta]1-transduced and antigen-activated BALB/c Th1 clones, specific for hemocyanin or ovalbumin, did not ameliorate EAE. Spinal cords from mice, taken 12 days after receiving TGF-[Beta]1-transduced, antigen-activated cells, contained detectable amounts of TGF-[Beta]1 cDNA. We conclude that latent TGF-[Beta]1-transduced, self-reactive T cell clones may be useful in the therapy of autoimmune diseases.