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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
Author(s) -
GEENEN V,
LOUIS C,
MARTENS H
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1337.008
Subject(s) - peripheral blood mononuclear cell , cytokine , immunology , insulin , peripheral , peripheral blood , medicine , growth factor , antigen presentation , antigen , immune system , endocrinology , chemistry , t cell , biochemistry , in vitro , receptor
A bstract : 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 β‐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 B9‐23, 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‐γ ( 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.