期刊
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
卷 90, 期 3, 页码 -出版社
WILEY
DOI: 10.1111/sji.12794
关键词
cytokines; experimental animals; natural killer T cells; transcription factors
类别
资金
- Swedish Cancer Society
- Swedish Research Council
- Strategic Research Center for Mucosal Immunobiology and Vaccines (MIVAC)
- Adlerbert Research Foundation
- Wilhelm and Martina Lundgrens Science Foundation
Natural killer T (NKT) cells are alpha beta T cell receptor (TCR) expressing innate-like T cells that display natural killer (NK) cell markers. Based on TCR characteristics, they are divided into two groups restricted to the MHC class I-like molecule CD1d. Type I NKT cells, most extensively studied, are identified by a semi-invariant V alpha 14-J alpha 18 (mouse, V alpha 24-J alpha 18 in humans) TCR reactive to the prototypic ligand alpha-galactosylceramide presented on CD1d. In contrast, type II NKT cells display diverse TCR reacting to different CD1d-presented ligands. There are no reagents that identify all type II NKT cells, limiting their exploration. Here, we searched for novel type II NKT cells by comparing J alpha 18(-/-)MHCII(-/-) mice that harbour type II but not type I NKT cells, and CD1d(-/-)MHCII(-/-) mice, lacking all NKT cells. We identified significantly larger populations of CD4(+) and CD4(-)CD8(-) (double negative, DN) TCR beta(+) cells expressing NKG2D or NKG2A/C/E in J alpha 18(-/-)MHCII(-/-) mice compared with CD1d(-/-)MHCII(-/-) mice, suggesting that 30%-50% of these cells were type II NKT cells. They expressed CD122, NK1.1, CXCR3 and intermediate/low levels of CD45RB. Further, the CD4(+) subset was CD69(+), while the DN cells were CD49b(+) and CD62L(+). Both subsets expressed the NKT cell-associated promyelocytic leukaemia zinc finger (PLZF) transcription factor and Tbet, while fewer cells expressed ROR gamma t. NKG2D(+) CD4(+) and DN populations were producers of IFN-gamma, but rarely IL-4 and IL-17. Taken together, we identify a novel subset of primary CD4(+) and DN type II NKT cells that expresses NKG2 receptors have typical NKT cell phenotypes and a TH1-like cytokine production.
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