title: Characterization of human invariant natural killer T cells expressing FoxP3.
abstract: Recently described forkhead box protein 3 (FoxP3) transcription factor is a key molecule in CD4+ CD25hi+ T-cell characterization. Invariant NK T (iNKT) cells are also characterized as regulatory cells modulating the immune response by rapidly producing T(h)1 and T(h)2 cytokines. We aimed to analyze cellular markers important in regulatory features of human iNKT cells and to study their role in functional assays. iNKT cells were single cell sorted from peripheral mononuclear cells of healthy individuals after immunostaining of invariant TCR α-chain. We found FoxP3 expression in human iNKT clones. Randomly selected iNKT cell clones (CD4+, double negative, CD8+) expressed FoxP3 mRNA and protein at different levels upon stimulation as supported by various approaches. FoxP3 mRNA and protein expression was detected in unstimulated iNKT cells as well. Furthermore, different stimulations changed the FoxP3 expression in iNKT cells over time and the most dramatic changes were observed upon anti-CD3 stimulation. Both the supernatant of iNKT cells and iNKT cells themselves exerted similar stimulation effects on PBMC proliferation in functional assays and these stimulations showed a negative correlation with FoxP3 expression. Our data indicate that the FoxP3 expression in iNKT cells may be a key transcriptional factor in controlling the regulatory function of the iNKT cells.
authors.affiliation: Section for Immunology and Immunogenetics, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Péter
authors.initials: P
authors.lastname: Engelmann
authors.forename: Klára
authors.initials: K
authors.lastname: Farkas
authors.forename: János
authors.initials: J
authors.lastname: Kis
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Richman
authors.forename: Zhaoyun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chong Wee
authors.initials: CW
authors.lastname: Liew
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
authors.forename: Monika A
authors.initials: MA
authors.lastname: Niewczas
authors.forename: Heyam
authors.initials: H
authors.lastname: Jalahej
authors.forename: Tihamér
authors.initials: T
authors.lastname: Orbán
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D000939:Epitopes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger