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Identification of distinct human invariant natural killer T-cell response phenotypes to alpha-galactosylceramide.

Croudace, Joanne E. and Curbishley, Stuart M and Mura, Manuela and Willcox, Carrie R and Illarianov, Petr A and Besra, Gurdyal S and Adams, David H and Lammas, David A (2008) Identification of distinct human invariant natural killer T-cell response phenotypes to alpha-galactosylceramide. Bmc Immunology, 9 (71). ISSN 1471-2172

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URL of Published Version: http://www.biomedcentral.com/content/pdf/1471-2172-9-71.pdf

Identification Number/DOI: 10.1186/1471-2172-9-71

Background

Human CD1d-restricted, invariant natural killer T cells (iNKT) are a unique class of T lymphocytes that recognise glycolipid antigens such as α-galactosylceramide (αGalCer) and upon T cell receptor (TCR) activation produce both Th1 and Th2 cytokines. iNKT cells expand when cultured in-vitro with αGalCer and interleukin 2 (IL-2) in a CD1d-restricted manner. However, the expansion ratio of human iNKT cells varies between individuals and this has implications for attempts to manipulate this pathway therapeutically. We have studied a panel of twenty five healthy human donors to assess the variability in their in-vitro iNKT cell expansion responses to stimulation with CD1d ligands and investigated some of the factors that may influence this phenomenon.

Results
Although all donors had comparable numbers of circulating iNKT cells their growth rates in-vitro over 14 days in response to a range of CD1d ligands and IL-2 were highly donor-dependent. Two reproducible donor response patterns of iNKT expansion were seen which we have called 'strong' or 'poor' iNKT responders. Donor response phenotype did not correlate with age, gender, frequency of circulating iNKT, or with the CD1d ligand utilised. Addition of exogenous recombinant human interleukin 4 (IL-4) to 'poor' responder donor cultures significantly increased their iNKT proliferative capacity, but not to levels equivalent to that of 'strong' responder donors. However in 'strong' responder donors, addition of IL-4 to their cultures did not significantly alter the frequency of iNKT cells in the expanded CD3+ population.

Conclusion
(i) in-vitro expansion of human iNKT cells in response to CD1d ligand activation is highly donor variable, (ii) two reproducible patterns of donor iNKT expansion were observed, which could be classified into 'strong' and 'poor' responder phenotypes, (iii) donor iNKT response phenotypes did not correlate with age, gender, frequency of circulating iNKT cells, or with the CD1d ligand utilised, (iv) addition of IL-4 to 'poor' but not 'strong' responder donor cultures significantly increased their in-vitro iNKT cell expansion to αGalCer.

Type of Work:Article
Date:2008 (Publication)
School/Faculty:Schools (1998 to 2008) > School of Biosciences
Department:MRC Centre for Immune Regulation,, Molecular Microbiology
Subjects:R Medicine (General)
Institution:University of Birmingham
Copyright Holders:BioMed Central
ID Code:139
Refereed:YES
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