Induction of differentiation of pre-NKT cells to mature Vα14 NKT cells by granulocyte/macrophage colony-stimulating factor

Abstract

Besides their unique developmental properties, V␣14 NKT cells are shown to recognize glycolipid antigens in the context with a monomorphic CD1d (6, 7), whose mode of antigen recognition is entirely distinct from that of conventional T cells that recognize peptide antigens in association with the MHC, which is polymorphic in nature. Therefore, NKT cells seem to constitute a novel immune system mainly against glycolipid antigens. Moreover, V␣24J␣Q T cells, a human counterpart for V␣14 NKT cells, have been identified (1) and are shown to recognize CD1d molecules (8,9). The conservation of the invariant V␣14 NKT cell receptor and of the recognition of CD1d ligand through evolution implies a critical role of V␣14 NKT cells in a host-defense system.A great deal of effort has been made to identify the molecules essential for the development of V␣14 NKT cells. In particular, studies with various genetically manipulated mice have revealed that NKT cell development depends on the molecules, including ␤ 2 -microglobulin (␤ 2 m) (10-12), CD1d (13-15), pT␣ (16), RAG-1 and 2 (17), TCF-1 (18), and J␣281 (4). These results suggest that V␣14 NKT cells are differentiated through selection events mediated by various cell surface receptors, such as mature or immature forms of NKT cell antigen receptors and cytokine receptors during the interaction with CD1d-expressing stroma cells. However, neither precursor populations nor precise molecular requirement for the development of V␣14 NKT cells has been clarified.Such emerging views on a novel subset of lymphocytes prompted us to search for their precursors and molecular requirements for NKT cell differentiation. Here, we have identified a precursor of mature V␣14 NKT cells and characterized the molecular requirements for differentiation. In addition, granulocyte͞macrophage colony-stimulating factor (GM-CSF) is found to be a critical molecule for the initiation of the V␣14 NKT receptor gene rearrangement during the development of these lymphocytes. MATERIALS AND METHODSMice. C57BL͞6 mice were obtained from Japan SLC (Hamamatsu, Japan). V␤8.2 transgenic (V␤8.

Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus

“…In the current study, we found that injection of mice with poly(I-C), a well-known and commonly used inducer of IFN-␣/␤, also caused a substantial loss of NKT cells ( (34,39), and IL-15 can induce the generation of pre-NKT cells into mature NKT cells (52), making it unlikely that an increase in IL-15 would cause a selective loss of NKT cells. IL-12 has been reported to cause a rapid reduction in NKT cells (18).…”

Overexpression of IL-15 In Vivo Enhances Tc1 Response, Which Inhibits Allergic Inflammation in a Murine Model of Asthma

“…This may be due to incomplete depletion of CD8 ϩ T cells by in vivo administration of anti-CD8 mAb. NK cells (13,35), NK T cells (36,37), and a significant fraction of ␥␦ T cells (26, 27, 38 -42) are also reported to respond to IL-15. Thus, early production of IFN-␥ by these cells, besides CD8 ϩ T cells, may be also responsible for the impaired Th2 responses in IL-15-Tg mice.…”

Impaired Proliferative Response of Vα24 NKT Cells from Cancer Patients Against α-Galactosylceramide

“…G-CSF and GM-CSF are cytokines produced by activated T cells, macrophages, endothelial cells, and stromal fibroblasts that act on bone marrow to increase the production of inflammatory leukocytes (21). GM-CSF was reported to be a critical molecule for the initiation of TCR gene rearrangement in V␣14 NKT cells during the development of these lymphocytes (22). It was reported that mRNA of the mouse G-CSF receptor was expressed in mouse NKT cells (23).…”