title: Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance.
abstract: A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4(+)Foxp3(+) cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3(hCD2) mice to isolate and ablate Foxp3(+) T reg cells with an anti-hCD2 antibody, we show for the first time that CD4(+)Foxp3(+) cells are crucial for infectious tolerance induced by nonablative anti-T cell antibodies. In tolerant animals, Foxp3(+) T reg cells are constantly required to suppress effector T cells still capable of causing tissue damage. Tolerated tissue contains T cells that are capable of rejecting it, but are prevented from doing so by therapeutically induced Foxp3(+) T reg cells. Finally, Foxp3(+) cells have been confirmed as the critical missing link through which infectious tolerance operates in vivo. Peripherally induced Foxp3(+) cells sustain tolerance by converting naive T cells into the next generation of Foxp3(+) cells. Empowering Foxp3(+) regulatory T cells in vivo offers a tractable route to avoid and correct tissue immunopathology.
authors.affiliation: Sir William Dunn School of Pathology, Oxford University, Oxford OX1 3RE, England, UK.
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Kendal
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Frederico S
authors.initials: FS
authors.lastname: Regateiro
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ma
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Adams
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Cobbold
authors.forename: Shohei
authors.initials: S
authors.lastname: Hori
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D017634:Self Tolerance / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D000906:Antibodies; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018398:Homeodomain Proteins; C064658:RAG-1 protein