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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/61494

Title: Distinct and Overlapping Effector Functions of Expanded Human CD4, CD8α and CD4CD8α Invariant Natural Killer T Cells
Author: ATZBERGER, ANN
JACKSON, JOHN
O'REILLY, VINCENT
DOHERTY, DEREK
FEIGHERY, CONLETH FRANCIS
ZENG, SHIJUAN GRACE
Sponsor: 
Name Grant Number
PHD/2004/2
05/RFP/BIC0015

Author's Homepage: http://people.tcd.ie/dohertde
http://people.tcd.ie/atzberga
http://people.tcd.ie/jjackso2
http://people.tcd.ie/cfighery
http://people.tcd.ie/zengsg
Keywords: Immunology
Invariant Natural Killer T Cells
Issue Date: 2011
Citation: O'Reilly V, Zeng SG, Bricard G, Atzberger A, Hogan AE, Jackson J, Feighery C, Porcelli SA, Doherty DG, Distinct and Overlapping Effector Functions of Expanded Human CD4, CD8α and CD4CD8α Invariant Natural Killer T Cells, PloS one, 6, 12, e28648, 2011
Series/Report no.: PloS one;
6;
12, e28648;
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.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/61494
Related links: http://dx.doi.org/10.1371/journal.pone.0028648
Appears in Collections:Immunology (Scholarly Publications)

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