Specific immunosuppression with inducible Foxp3-transduced polyclonal T cells.
Forkhead box p3 (Foxp3)-expressing regulatory T cells are key mediators of peripheral tolerance suppressing undesirable immune responses. Ectopic expression of Foxp3 confers regulatory T cell phenotype to conventional T cells, lending itself to therapeutic use in the prevention of autoimmunity and transplant rejection. Here, we show that adoptive transfer of polyclonal, wild-type T cells transduced with an inducible form of Foxp3 (iFoxp3) can be used to suppress immune responses on demand. In contrast to Foxp3-transduced cells, iFoxp3-transduced cells home "correctly" into secondary lymphoid organs, where they expand and participate in immune responses. Upon induction of iFoxp3, the cells assume regulatory T cell phenotype and start to suppress the response they initially partook in without causing systemic immunosuppression. We used this approach to suppress collagen-induced arthritis, in which conventional Foxp3-transduced cells failed to show any effect. This provides us with a generally applicable strategy to specifically halt immune responses on demand without prior knowledge of the antigens involved.
Andersen
Kristian G
KG
Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom.
Butcher
Tracey
T
Betz
Alexander G
AG
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D003094:Collagen / Q000008:administration & dosage; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy; D009052:Leukemia Virus, Murine / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014161:Transduction, Genetic
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D003094:Collagen