학술논문

Distinct Cytokine Profiles of Neonatal Natural Killer T Cells after Expansion with Subsets of Dendritic Cells
Document Type
article
Source
Journal of Experimental Medicine. 193(10)
Subject
Infectious Diseases
Aetiology
2.1 Biological and endogenous factors
1.1 Normal biological development and functioning
Underpinning research
Inflammatory and immune system
Adult
Autoimmune Diseases
CD28 Antigens
CD3 Complex
Cytokines
Dendritic Cells
Fetal Blood
Graft vs Host Disease
Humans
Infant
Newborn
Interferon-gamma
Interleukin-2
Interleukin-4
Interleukin-7
Killer Cells
Natural
Lymphocyte Activation
Phytohemagglutinins
T-Lymphocyte Subsets
cord blood
interleukin 4
interferon gamma
autoimmune diseases
graft versus host disease
Medical and Health Sciences
Immunology
Language
Abstract
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.