title: The cellular prion protein is preferentially expressed by CD4+ CD25+ Foxp3+ regulatory T cells.
abstract: Post-translational modification of the cellular prion protein (PrP(C)) is intimately associated with the pathogenesis of prion disease, yet the normal function of the protein remains unclear. PrP(C) is expressed in lymphoid cells and is known to be a T-cell activation antigen. Further, transcription profiling studies of regulatory T cells have shown preferential overexpression of PrP(C), suggesting a possible role in regulatory function. We report that both the expression of PrP message and cell surface PrP(C) levels are increased in murine CD4(+) CD25(+) regulatory T cells compared with CD4(+) CD25(-) cells. However, PrP(0/0) mice do not show altered regulatory T-cell numbers or forkhead box P3 (Foxp3) expression levels, or impaired regulatory T-cell function in vitro. Nevertheless, the preferential expression of surface PrP(C) by regulatory T cells raises the possibility that therapeutic ligation of PrP(C) might alter immune regulation.
authors.affiliation: Department of Infectious Diseases and Immunity, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Isaacs
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Garden
authors.forename: Gurman
authors.initials: G
authors.lastname: Kaur
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.forename: Graham S
authors.initials: GS
authors.lastname: Jackson
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Altmann
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000032:analysis*; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D018621:PrPC Proteins