title: A natural killer T (NKT) cell developmental pathway iInvolving a thymus-dependent NK1.1(-)CD4(+) CD1d-dependent precursor stage.
abstract: The development of CD1d-dependent natural killer T (NKT) cells is poorly understood. We have used both CD1d/alpha-galactosylceramide (CD1d/alphaGC) tetramers and anti-NK1.1 to investigate NKT cell development in vitro and in vivo. Confirming the thymus-dependence of these cells, we show that CD1d/alphaGC tetramer-binding NKT cells, including NK1.1(+) and NK1.1(-) subsets, develop in fetal thymus organ culture (FTOC) and are completely absent in nude mice. Ontogenically, CD1d/alphaGC tetramer-binding NKT cells first appear in the thymus, at day 5 after birth, as CD4(+)CD8(-)NK1.1(-)cells. NK1.1(+) NKT cells, including CD4(+) and CD4(-)CD8(-) subsets, appeared at days 7-8 but remained a minor subset until at least 3 wk of age. Using intrathymic transfer experiments, CD4(+)NK1.1(-) NKT cells gave rise to NK1.1(+) NKT cells (including CD4(+) and CD4(-) subsets), but not vice-versa. This maturation step was not required for NKT cells to migrate to other tissues, as NK1.1(-) NKT cells were detected in liver and spleen as early as day 8 after birth, and the majority of NKT cells among recent thymic emigrants (RTE) were NK1.1(-). Further elucidation of this NKT cell developmental pathway should prove to be invaluable for studying the mechanisms that regulate the development of these cells.
authors.affiliation: Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
authors.forename: Kirsten J L
authors.initials: KJ
authors.lastname: Hammond
authors.forename: Adam P
authors.initials: AP
authors.lastname: Uldrich
authors.forename: Alan G
authors.initials: AG
authors.lastname: Baxter
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D055610:Antigens, CD1d; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D005333:Fetus; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008099:Liver / Q000254:growth & development / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011498:Protein Precursors / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013154:Spleen / Q000196:embryology / Q000254:growth & development / Q000276:immunology; D013950:Thymus Gland / Q000196:embryology / Q000254:growth & development / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D015704:CD4 Antigens; D016207:Cytokines; D011498:Protein Precursors; D016693:Receptors, Antigen, T-Cell, alpha-beta