Analysis of roles of GM-CSF for proliferation and differentiation of NKT cells

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This work aimed to analyze effects of GM-CSF for proliferation and differentiation of NKT cells using transgenic mice expressing human GM-CSF receptor. GM-CSF was reported to be a maturation factor for NKT cell i. e. TCR a chain recombination inducing factor, by Dr. Taniguchi' group. We administrated GM-CSF into transgenic mice expressing human GM-CSF receptor, and found that the population of NKT cells has not been changed but the total number of spleen cells was dramatically increased. This observation suggested that GM-CSF acts as a proliferation promoting factor for NKT cells. Since we previously reported that GM-CSF induced proliferation of myeloid cells but not lymphoid cells, it is notable that NKT cells respond to GM-CSF as myeloid cells but not like lymphoid cells. The effects of GM-CSF for NKT cells was reported not only for spleen but also thymus, bone marow. We also observed that in vivo administration of GM-CSF increased NKT cells in these organs, suggesting effects of GM-CSF for NKT cells is not spleen specific. To analyze the mechanism of GM-CSF effects on NKT cells, we made double transgenic mice expressing both human GM-CSF receptor and TCRb8.2. We isolated precursor cell of NKT cells and succeeded to culture these cells in vitro. This system makes it possible to analyze molecular mechanism of NKT cell differentiation and proliferation. Furthermore, we established ES cells expressing GM-CSF receptor or its mutant stably. Using these ES cells, we are planning to make transgenic mice, and also to try in vitro differentiation of NKT cells from ES cells by using GM-CSF signals.