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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bagchi, Sreya Wang, Chyung-ru Weng, Xiufang Zhao, Jie |
| Description | Author Affiliation: Zhao J ( Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.); |
| Abstract | CD1d-restricted natural killer T (NKT) cells are innate-like T cells with potent immunomodulatory function via rapid production of both Th1 and Th2 cytokines. NKT cells comprise well-characterized type I NKT cells, which can be detected by -galactosylceramide-loaded CD1d tetramers, and less-studied type II NKT cells, which do not recognize -galactosylceramide. Here we characterized type II NKT cells on a polyclonal level by using a J 18-deficient IL-4 reporter mouse model. This model allows us to track type II NTK cells by the GFP(+)TCRß(+) phenotype in the thymus and liver. We found type II NKT cells, like type I NKT cells, exhibit an activated phenotype and are dependent on the transcriptional regulator promyelocytic leukemia zinc finger (PLZF) and the adaptor molecule signaling lymphocyte activation molecule-associated protein (SAP) for their development. Type II NKT cells are potently activated by ß-D-glucopyranosylceramide (ß-GlcCer) but not sulfatide or phospholipids in a CD1d-dependent manner, with the stimulatory capacity of ß-GlcCer influenced by acyl chain length. Compared with type I NKT cells, type II NKT cells produce lower levels of IFN-γ but comparable amounts of IL-13 in response to polyclonal T-cell receptor stimulation, suggesting they may play different roles in regulating immune responses. Furthermore, type II NKT cells can be activated by CpG oligodeoxynucletides to produce IFN-γ, but not IL-4 or IL-13. Importantly, CpG-activated type II NKT cells contribute to the antitumor effect of CpG in the B16 melanoma model. Taken together, our data reveal the characteristics of polyclonal type II NKT cells and their potential role in antitumor immunotherapy. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Immunomodulation Immunology Intracellular Signaling Peptides And Proteins Metabolism Kruppel-Like Transcription Factors Melanoma, Experimental Natural Killer T-Cells Animals CpG Islands Genetics DNA Primers Flow Cytometry Green Fluorescent Proteins Therapy Mice Mice, Knockout Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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