F.72. IL-1 beta produced in response to islet autoantigen presentation differentiates T-helper-17 cells at the expense of regulatory T cells: Implications for the timing of tolerizing immunotherapy

Bertin-Maghit, Sebastien, O'Sullivan, Brendan, Best, Shannoiin, Duggan, Emily, Pang, Dimeng, Thomas, Helen, Kay, Thomas, Harrison, Leonard, Steptoe, Raymond and Thomas, Ranjeny (2010). F.72. IL-1 beta produced in response to islet autoantigen presentation differentiates T-helper-17 cells at the expense of regulatory T cells: Implications for the timing of tolerizing immunotherapy. In: FOCIS 2010 Abstract Supplement :10th Annual Meeting, Federation of Clinical Immunology Societies. FOCiS 2010: Tenth Annual Meeting of the Federation of Clinical Immunology Societies, Boston, MA, U.S.A., (S98-S98). 24-27 June 2010. doi:10.1016/j.clim.2010.03.294


Author Bertin-Maghit, Sebastien
O'Sullivan, Brendan
Best, Shannoiin
Duggan, Emily
Pang, Dimeng
Thomas, Helen
Kay, Thomas
Harrison, Leonard
Steptoe, Raymond
Thomas, Ranjeny
Title of paper F.72. IL-1 beta produced in response to islet autoantigen presentation differentiates T-helper-17 cells at the expense of regulatory T cells: Implications for the timing of tolerizing immunotherapy
Formatted title
F.72. IL-1β produced in response to islet autoantigen presentation differentiates T-helper-17 cells at the expense of regulatory T cells: Implications for the timing of tolerizing immunotherapy
Conference name FOCiS 2010: Tenth Annual Meeting of the Federation of Clinical Immunology Societies
Conference location Boston, MA, U.S.A.
Conference dates 24-27 June 2010
Proceedings title FOCIS 2010 Abstract Supplement :10th Annual Meeting, Federation of Clinical Immunology Societies   Check publisher's open access policy
Journal name Clinical Immunology   Check publisher's open access policy
Place of Publication Orlando, FL, U.S.A.
Publisher Academic Press
Publication Year 2010
Sub-type Published abstract
DOI 10.1016/j.clim.2010.03.294
ISSN 1521-6616
1521-7035
Volume 135
Issue Supp. 1
Start page S98
End page S98
Total pages 1
Collection year 2011
Language eng
Formatted Abstract/Summary
The effectiveness of tolerizing immunotherapeutic strategies, such as anti-CD40L or dendritic cells (DC), is greater when administered to young NOD mice than at peak insulitis. RelBlo DC, generated in the presence of an NF-κB inhibitor, induce T regulatory (Treg) cells and suppress inflammation in a model of rheumatoid arthritis. IL-1β is over-expressed in humans and mice at risk of T1DM, dysregulates Treg cells, and accelerates diabetes in NOD mice. We investigated the relationship between IL-1β production and the response to RelBlo DC in the pre-diabetic period. We injected RelBlo DC s.c. into 4- or 14-week-old NOD mice, and tracked the incidence of diabetes and effect on Treg cell function. We measured IL-1β production by stimulated splenocytes from mice of different ages and strains, and proliferative and cytokine responses of T effectors to Treg in vitro. Tolerising RelBlo DC significantly inhibited diabetes progression when administered to 4-week-old but not 14 week old mice. IL-1β production by NOD splenocytes was increased from 6 to 16 weeks of age, when MHC-restricted islet antigen presentation to autoreactive T cells occurred. IL-1 promoted Th17 cells and reduced the capacity of Treg cells to suppress effector cells. RelBlo DC exacerbated the IL-1-dependent decline in Treg function and promoted Th17. IL-1β, generated by islet-autoreactive cells in MHC-susceptible mice, accelerates diabetes by differentiating Th17 at the expense of Treg. Tolerizing DC-therapies can regulate islet autoantigen priming and prevent diabetes, but progression past the IL-1β/IL-17 checkpoint signals the need for other strategies.
Subjects 1107 Immunology
Keyword Immunotherapy
T cell
Q-Index Code EX
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Shannon Best's name is misspelt on this abstract.

Document type: Conference Paper
Collections: Non HERDC
UQ Diamantina Institute Publications
 
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Created: Sun, 29 Aug 2010, 00:07:31 EST