title: Phenotypical and functional alterations during the expansion phase of invariant Valpha14 natural killer T (Valpha14i NKT) cells in mice primed with alpha-galactosylceramide.
abstract: Invariant Valpha14 natural killer T (Valpha14i NKT) cells are a unique immunoregulatory T-cell population that is restricted by CD1d. The glycolipid alpha-galactosylceramide (alpha-GalCer) is presented by CD1d and causes robust Valpha14i NKT-cell activation. Three days after injection of alpha-GalCer, Valpha14i NKT cells vigorously increase in number and then gradually decrease to normal levels. In the present study, we found that the re-administration of alpha-GalCer into mice primed 3 days earlier causes a marked increase in serum interleukin-4 and interferon-gamma. Intracellular staining revealed that the only expanded Valpha14i NKT cells are responsible for the enhanced cytokine production. The enhanced cytokine production was correlated with an increased number of Valpha14i NKT cells after priming. Additionally, primed Valpha14i NKT cells produced larger amounts of cytokine as compared with naive Valpha14i NKT cells when cultured with alpha-GalCer-pulsed dendritic cells. Thus, we considered that a subset of expanded Valpha14i NKT cells acquired a strong ability to produce cytokines. In contrast to mice primed 3 days earlier, cytokine production is markedly diminished in mice primed 7 days earlier. The expanded Valpha14i NKT cells altered the surface phenotype (NK1.1- CD69-) and contained intracellular interferon-gamma. Additionally, we found that primed Valpha14i NKT cells did not disappear or down-regulate surface TCR expression when re-injected with alpha-GalCer as compared with naive Valpha14i NKT cells. These results demonstrate that the function and surface phenotype of Valpha14i NKT cells is dramatically altered after alpha-GalCer priming.
authors.affiliation: Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Akira
authors.initials: A
authors.lastname: Iizuka
authors.forename: Yumie
authors.initials: Y
authors.lastname: Koshidaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Heike
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
authors.forename: Mitsuzi
authors.initials: M
authors.lastname: Yoshida
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Hiro
authors.initials: H
authors.lastname: Wakasugi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000097:blood; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood; D000954:Antigens, Surface / Q000097:blood; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005699:Galactosylceramides / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D016207:Cytokines; D005699:Galactosylceramides; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C493154:alpha-galactosylceramide; C045084:invariant chain