title: Innate-like effector differentiation of human invariant NKT cells driven by IL-7.
abstract: Conventional MHC-restricted T lymphocytes leave thymus with a naive phenotype and require Ag-dependent stimulation coupled to proliferation to acquire effector functions. Invariant (i)NKT cells are a subset of T lymphocytes considered innate because they display an effector memory phenotype independent of TCR stimulation by foreign Ags. We investigated the effector differentiation program followed by human iNKT cells by studying cells from a relevant set of fetal thymi and umbilical cord blood samples. We find that human fetal iNKT cells have already started a differentiation program that activates the epigenetic and transcriptional control of ifng and il4 genes, leading at birth to cells that express these cytokines upon TCR signaling but independently of proliferation in vitro. Both ex vivo and in vitro analysis of fetal and neonatal iNKT cells delineate an effector differentiation program linked to cell division in vivo, and they identify IL-7 as one of the crucial signals driving this program in the apparent absence of Ag stimulation. Consistent with these data, human fetal and neonatal iNKT cells are hyperresponsive in vitro to IL-7 in comparison to conventional T cells, owing to an increased expression and signaling function of the IL-7 receptor alpha-chain. The innate nature of human iNKT cells could thus derive from lineage-specific developmental cues that selectively make these cells efficient IL-7 responders following thymic selection.
authors: Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, DIBIT, San Raffaele Scientific Institute, Milan, Italy. delalla.claudia@hsr.it
authors: Claudia
authors: C
authors: de Lalla
authors: Nicola
authors: N
authors: Festuccia
authors: Inka
authors: I
authors: Albrecht
authors: Hyun-Dong
authors: HD
authors: Chang
authors: Grazia
authors: G
authors: Andolfi
authors: Ulrike
authors: U
authors: Benninghoff
authors: Ferdinando
authors: F
authors: Bombelli
authors: Giovanna
authors: G
authors: Borsellino
authors: Alessandro
authors: A
authors: Aiuti
authors: Andreas
authors: A
authors: Radbruch
authors: Paolo
authors: P
authors: Dellabona
authors: Giulia
authors: G
authors: Casorati
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D044127:Epigenesis, Genetic / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology*; D007231:Infant, Newborn; D015851:Interleukin-7 / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D016207:Cytokines; D015851:Interleukin-7