title: CD4+CD25+CD127dimFoxp3+ T cells are cytotoxic for human neurons.
abstract: MS lesions are characterized by destruction of myelin and significant neuronal and axonal loss. Preliminary studies with the use of T(regs) in the mouse model of MS have been extremely encouraging. However, recent studies with human cells have shown the presence of different subpopulations of T cells within the CD4(+)CD25(+)Foxp3(+) T cell phenotype, some of which do not have regulatory functions. These findings suggest a potential difference between mouse and human in the regulatory phenotype. Here, we show that human activated CD4(+)CD25(+)Foxp3(+) T cells are neurotoxic in vitro. These cells expressed high levels of the cytotoxic molecule GrB and had no suppressive effect. On the contrary, they produced IFN-γ and low IL-17, suggesting a shift toward a T(H)1 phenotype. Thus, our data confirm the presence of a nonregulatory cytotoxic subpopulation within the human CD4(+)CD25(+)Foxp3(+) T cells and suggest further studies on the human regulatory phenotype prior to any potential therapeutic application.
authors.affiliation: Division of Neurology/Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada.
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Haile
authors.forename: Dion
authors.initials: D
authors.lastname: Pasychniyk
authors.forename: Diane
authors.initials: D
authors.lastname: Turner
authors.forename: R Chris
authors.initials: RC
authors.lastname: Bleackley
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giuliani
mesh_terms: D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D009474:Neurons / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D012333:RNA, Messenger