Distinct cytokine profiles of neonatal natural killer T cells after expansion with subsets of dendritic cells.
Natural killer T (NKT) cells are a highly conserved subset of T cells that have been shown to play a critical role in suppressing T helper cell type 1-mediated autoimmune diseases and graft versus host disease in an interleukin (IL)-4-dependent manner. Thus, it is important to understand how the development of IL-4- versus interferon (IFN)-gamma-producing NKT cells is regulated. Here, we show that NKT cells from adult blood and those from cord blood undergo massive expansion in cell numbers (500-70,000-fold) during a 4-wk culture with IL-2, IL-7, phytohemagglutinin, anti-CD3, and anti-CD28 mAbs. Unlike adult NKT cells that preferentially produce both IL-4 and IFN-gamma, neonatal NKT cells preferentially produce IL-4 after polyclonal activation. Addition of type 2 dendritic cells (DC2) enhances the development of neonatal NKT cells into IL-4(+)IFN-gamma(-) NKT2 cells, whereas addition of type 1 dendritic cells (DC1) induces polarization towards IL-4(-)IFN-gamma(+) NKT1 cells. Adult NKT cells display limited plasticity for polarization induced by DC1 or DC2. Thus, newly generated NKT cells may possess the potent ability to develop into IL-4(+)IFN-gamma(-) NKT2 cells in response to appropriate stimuli and may thereafter acquire the tendency to produce both IL-4 and IFN-gamma.
Kadowaki
N
N
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Antonenko
S
S
Ho
S
S
Rissoan
M C
MC
Soumelis
V
V
Porcelli
S A
SA
Lanier
L L
LL
Liu
Y J
YJ
D000328:Adult; D001327:Autoimmune Diseases / Q000209:etiology; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2; D015847:Interleukin-4 / Q000378:metabolism; D015851:Interleukin-7; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D010835:Phytohemagglutinins; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D015851:Interleukin-7; D010835:Phytohemagglutinins; D015847:Interleukin-4; D007371:Interferon-gamma