title: Naive regulatory T cells: a novel subpopulation defined by resistance toward CD95L-mediated cell death.
abstract: Most CD4(+)CD25(hi)FOXP3(+) regulatory T cells (T(regs)) from adult peripheral blood express high levels of CD45RO and CD95 and are prone to CD95L-mediated apoptosis in contrast to conventional T cells (T(convs)). However, a T(reg) subpopulation remained consistently apoptosis resistant. Gene microarray and 6-color flow cytometry analysis including FOXP3 revealed an increase in naive T-cell markers on the CD95L-resistant T(regs) compared with most T(regs). In contrast to T(regs) found in adult humans, most CD4(+)CD25(+)FOXP3(+) T cells found in cord blood are naive and exhibit low CD95 expression. Furthermore, most of these newborn T(regs) are not sensitive toward CD95L similar to naive T(regs) from adult individuals. After short stimulation with anti-CD3/CD28 monoclonal antibodies (mAbs), cord blood T(regs) strongly up-regulated CD95 and were sensitized toward CD95L. This functional change was paralleled by a rapid up-regulation of memory T-cell markers on cord blood T(regs) that are frequently found on adult memory T(regs). In summary, we show a clear functional difference between naive and memory T(regs) that could result in different survival rates of those 2 cell populations in vivo. This new observation could be crucial for the planning of therapeutic application of T(regs).
authors.affiliation: Department of Neonatology, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany. benedikt.fritzsching@med.uni-heidelberg.de.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Fritzsching
authors.forename: Nina
authors.initials: N
authors.lastname: Oberle
authors.forename: Eva
authors.initials: E
authors.lastname: Pauly
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Johannes
authors.initials: J
authors.lastname: Poschl
authors.forename: Peter
authors.initials: P
authors.lastname: Krammer
authors.forename: Otwin
authors.initials: O
authors.lastname: Linderkamp
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Suri-Payer
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D002470:Cell Survival; D053222:Fas Ligand Protein; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D016131:Lymphocyte Subsets; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D015854:Up-Regulation; D019014:fas Receptor / Q000032:analysis
chemical_list: C418974:FOXP3 protein, human; D053222:Fas Ligand Protein; D051858:Forkhead Transcription Factors; D019014:fas Receptor