The cellular prion protein is preferentially expressed by CD4+ CD25+ Foxp3+ regulatory T cells.
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.
Isaacs
Jeremy D
JD
Department of Infectious Diseases and Immunity, Imperial College, Hammersmith Hospital, London, UK.
Garden
Oliver A
OA
Kaur
Gurman
G
Collinge
John
J
Jackson
Graham S
GS
Altmann
Daniel M
DM
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
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D018621:PrPC Proteins