O'Reilly, Vincent P. and Zeng, Shijuan G. and Bricard, Gabriel and Atzberger, Ann and Hogan, Andrew E. and Jackson, John and Feighery, Conleth and Porcelli, Steven A. and Doherty, Derek G. (2011) Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells. PLoS ONE, 6 (12). e28648. ISSN 1932-6203

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Abstract

CD1d-restricted invariant natural killer T (iNKT) cells have diverse immune stimulatory/regulatory activities through their ability to release cytokines and to kill or transactivate other cells. Activation of iNKT cells can protect against multiple diseases in mice but clinical trials in humans have had limited impact. Clinical studies to date have targeted polyclonal mixtures of iNKT cells and we proposed that their subset compositions will influence therapeutic outcomes. We sorted and expanded iNKT cells from healthy donors and compared the phenotypes, cytotoxic activities and cytokine profiles of the CD4+, CD8α+ and CD4−CD8α− double-negative (DN) subsets. CD4+ iNKT cells expanded more readily than CD8α+ and DN iNKT cells upon mitogen stimulation. CD8α+ and DN iNKT cells most frequently expressed CD56, CD161 and NKG2D and most potently killed CD1d+ cell lines and primary leukemia cells. All iNKT subsets released Th1 (IFN-γ and TNF-α) and Th2 (IL-4, IL-5 and IL-13) cytokines. Relative amounts followed a CD8α>DN>CD4 pattern for Th1 and CD4>DN>CD8α for Th2. All iNKT subsets could simultaneously produce IFN-γ and IL-4, but single-positivity for IFN-γ or IL-4 was strikingly rare in CD4+ and CD8α+ fractions, respectively. Only CD4+ iNKT cells produced IL-9 and IL-10; DN cells released IL-17; and none produced IL-22. All iNKT subsets upregulated CD40L upon glycolipid stimulation and induced IL-10 and IL-12 secretion by dendritic cells. Thus, subset composition of iNKT cells is a major determinant of function. Use of enriched CD8α+, DN or CD4+ iNKT cells may optimally harness the immunoregulatory properties of iNKT cells for treatment of disease.

Item Type:	Article
Additional Information:	© 2011 O'Reilly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Cite as: O'Reilly V, Zeng SG, Bricard G, Atzberger A, Hogan AE, Jackson J, et al. (2011) Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells. PLoS ONE 6(12): e28648. https://doi.org/10.1371/journal.pone.0028648
Keywords:	Distinct; Overlapping; Effector Functions; Expanded Human CD4+; CD8a+; CD4-CD8a-; Invariant Natural Killer T Cells;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12433
Identification Number:	https://doi.org/10.1371/journal.pone.0028648
Depositing User:	Andrew Hogan
Date Deposited:	17 Feb 2020 16:03
Journal or Publication Title:	PLoS ONE
Publisher:	Public Library of Science
Refereed:	Yes
Funders:	Health Research Board (HRB), Science Foundation Ireland (SFI), National Institute of Health
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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