The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
IL-21 Is Produced by NKT Cells and Modulates NKT Cell Activation and Cytokine Production
Abstract
The common γ-chain cytokine, IL-21, is produced by CD4+ T cells and mediates potent effects on a variety of immune cells including NK, T, and B cells. NKT cells express the receptor for IL-21; however, the effect of this cytokine on NKT cell function has not been studied. We show that IL-21 on its own enhances survival of NKT cells in vitro, and IL-21 increases the proliferation of NKT cells in combination with IL-2 or IL-15, and particularly with the CD1d-restricted glycosphingolipid Ag α-galactosylceramide. Similar to its effects on NK cells, IL-21 enhances NKT cell granular morphology, including granzyme B expression, and some inhibitory NK receptors, including Ly49C/I and CD94. IL-21 also enhanced NKT cell cytokine production in response to anti-CD3/CD28 in vitro. Furthermore, NKT cells may be subject to autocrine IL-21-mediated stimulation because they are potent producers of this cytokine following in vitro stimulation via CD3 and CD28, particularly in conjunction with IL-12 or following in vivo stimulation with α-galactosylceramide. Indeed, NKT cells produced much higher levels of IL-21 than conventional CD4 T cells in this assay. This study demonstrates that NKT cells are potentially a major source of IL-21, and that IL-21 may be an important factor in NKT cell-mediated immune regulation, both in its effects on NK, T, and B cells, as well as direct effects on NKT cells themselves. The influence of IL-21 in NKT cell-dependent models of tumor rejection, microbial clearance, autoimmunity, and allergy should be the subject of future investigations.
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Citations
Cites
CD1d-Restricted and TCR-Mediated Activation of V α 14 NKT Cells by Glycosylceramides
Kawano, T., Cui, J., Koezuka, Y., Toura, I., Kaneko, Y., Motoki, K., Ueno, H., Nakagawa, R., Sato, H., Kondo, E., et al. (1997) · Science · doi:10.1126/science.278.5343.1626 · Cited by 2,400
Requirement for V α 14 NKT Cells in IL-12-Mediated Rejection of Tumors
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Self-citationCD1: Antigen Presentation and T Cell Function
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A Critical Role for IL-21 in Regulating Immunoglobulin Production
Ozaki, K., Spolski, R., Feng, C. G., Qi, C.-F., Cheng, J., Sher, A., Morse, H. C., Liu, C., Schwartzberg, P. L., & Leonard, W. J. (2002) · Science · doi:10.1126/science.1077002 · Cited by 978
Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers
Matsuda, J. L., Naidenko, O. V., Gapin, L., Nakayama, T., Taniguchi, M., Wang, C.-R., Koezuka, Y., & Kronenberg, M. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.5.741 · Cited by 887
Going both ways: Immune regulation via CD1d-dependent NKT cells
Godfrey, D. I., & Kronenberg, M. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200423594 · Cited by 877
Self-citationCarnaud, C., Lee, D., Donnars, O., Park, S.-H., Beavis, A., Koezuka, Y., & Bendelac, A. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.9.4647 · Cited by 854
Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells
Smyth, M. J., Thia, K. Y. T., Street, S. E. A., Cretney, E., Trapani, J. A., Taniguchi, M., Kawano, T., Pelikan, S. B., Crowe, N. Y., & Godfrey, D. I. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.4.661 · Cited by 829
Self-citation
Cited by
IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses
Linterman, M. A., Beaton, L., Yu, D., Ramiscal, R. R., Srivastava, M., Hogan, J. J., Verma, N. K., Smyth, M. J., Rigby, R. J., & Vinuesa, C. G. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091738 · Cited by 801
Self-citationInterleukin-21: Basic Biology and Implications for Cancer and Autoimmunity
Spolski, R., & Leonard, W. J. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090316 · Cited by 696
Godfrey, D. I., Stankovic, S., & Baxter, A. G. (2010) · Nature Immunology · doi:10.1038/ni.1841 · Cited by 649
Self-citationT Follicular Helper (TFH) Cells in Normal and Dysregulated Immune Responses
King, C., Tangye, S. G., & Mackay, C. R. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090344 · Cited by 632
IL-21 Is Required to Control Chronic Viral Infection
Elsaesser, H., Sauer, K., & Brooks, D. G. (2009) · Science · doi:10.1126/science.1174182 · Cited by 554
Metadata
- Authors
- Coquet, J. M., Kyparissoudis, K., Pellicci, D. G., Besra, G., Berzins, S. P., Smyth, M. J., & Godfrey, D. I.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-03-01
- Volume
- 178
- Issue
- 5
- Pages
- 2827-2834
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2163992046
- Cited by
- 364
- References
- 58
- FWCI
- 13.16
- Type
- journal article
- Language
- en
- Open access
- closed
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- Coquet, J. M., Kyparissoudis, K., Pellicci, D. G., Besra, G., Berzins, S. P., Smyth, M. J., & Godfrey, D. I. (2007). IL-21 Is Produced by NKT Cells and Modulates NKT Cell Activation and Cytokine Production. The Journal of Immunology. https://doi.org/10.4049/jimmunol.178.5.2827
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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