title: Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo.
abstract: To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms of immunological memory. Factors regulating memory CD4(+) T helper (Th)-cell pool size and function remain unclear, however. We show that activation of type I invariant natural killer T (iNKT) cells with glycolipid ligands and activation of type II natural killer T (NKT) cells with the endogenous ligand sulfatide induced dramatic proliferation and expansion of memory, but not naïve, CD4 T cells. NKT cell-induced proliferation of memory Th1 and Th2 cells was dependent largely on the production of IL-2, with Th2-cell proliferation also affected by loss of IL-4. Type II NKT cells were also required for efficient maintenance of memory CD4 T cells in vivo. Activation of iNKT cells resulted in up-regulation of IFN-γ expression by memory Th2 cells. These IFN-γ-producing memory Th2 cells showed a decreased capability to induce Th2 cytokines and eosinophilic airway inflammation. Thus, activated NKT cells directly regulate memory CD4 T-cell pool size and function via the production of cytokines in vivo.
authors.affiliation: Department of Immunology, Graduate School of Medicine,  Chiba University, Chiba 260-8670,  Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Iwamura
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Endo
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Damon John
authors.initials: DJ
authors.lastname: Tumes
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawahara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kinjo
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects*; D006017:Glycolipids / Q000494:pharmacology; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D018418:Th2 Cells
chemical_list: D055610:Antigens, CD1d; D006017:Glycolipids; D007376:Interleukin-2; D013433:Sulfoglycosphingolipids; D015847:Interleukin-4; D007371:Interferon-gamma