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Correspondence to: Yong-Jun Liu, DNAX Research Institute, 901 California Ave., Palo Alto, CA 94304. Tel:650-496-1157 Fax:650-496-1200 E-mail:yliu{at}dnax.org.
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 1mediated autoimmune diseases and graft versus host disease in an interleukin (IL)-4dependent manner. Thus, it is important to understand how the development of IL-4 versus interferon (IFN)-
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 (50070,000-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-
, 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-
- NKT2 cells, whereas addition of type 1 dendritic cells (DC1) induces polarization towards IL-4-IFN-
+ 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-
- NKT2 cells in response to appropriate stimuli and may thereafter acquire the tendency to produce both IL-4 and IFN-
.
Key Words:
cord blood, interleukin 4, interferon
, autoimmune diseases, graft versus host disease
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