An insulin-like growth factor 2-derived self-antigen inducing a regulatory cytokine profile after presentation to peripheral blood mononuclear cells from DQ8(+) type 1 diabetic adolescents - Preliminary design of a thymus-based tolerogenic self-vaccination
Geenen, Vincent; Louis, Céline; Martens, Henri
2004 • In Annals of the New York Academy of Sciences, 1037, p. 59-64
thymus; type 1 diabetes; self-antigens; IGF-2; self-vaccination
Abstract :
[en] This work aims to evaluate the potential use of insulin-like growth factor 2 (IGF-2) as the dominant thymic self-antigen precursor of the insulin family in designing a tolerogenic approach to type 1 diabetes (T1D) prevention. This evaluation was primarily based on cytokine profile driven by MHC presentation of insulin and IGF-2-derived antigens to PBMC cultures derived from 16 T1D DQ8(+) adolescents. Insulin B9-23, one dominant P-cell autoantigen, and the homologous sequence B11-25 of IGF-2 display the same affinity and fully compete for binding to DQ8, a MHC-II allele conferring major genetic susceptibility to type 1 diabetes (T1D). However, compared to insulin beta 9-23, presentation of IGF-2 B11-25 elicits a suppressive/regulatory cytokine profile with a higher number of IL-10-secreting cells (P < 0.05), a much higher ratio of IL-10/IFN-gamma (P < 0.01), as well as a lower number of IL-4-secreting cells (P < 0.05). Thus, with regard to T1D prevention, administration of IGF-2-derived self-antigen(s) seems to be an efficient approach that combines both antagonism for binding to a major susceptibility MHC-II allele, as well as downstream promotion of an antigen-driven tolerogenic response.
Geenen, Vincent ; Université de Liège - ULiège > Centre d'immunologie
Louis, Céline ; Université de Liège - ULiège > Centre d'immunologie
Martens, Henri ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Embryologie
Language :
English
Title :
An insulin-like growth factor 2-derived self-antigen inducing a regulatory cytokine profile after presentation to peripheral blood mononuclear cells from DQ8(+) type 1 diabetic adolescents - Preliminary design of a thymus-based tolerogenic self-vaccination
Publication date :
December 2004
Journal title :
Annals of the New York Academy of Sciences
ISSN :
0077-8923
eISSN :
1749-6632
Publisher :
New York Acad Sciences, New York, United States - New York
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