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.
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 beta-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-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
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V
Liège University Center of Immunology (CIL), Institute of Pathology CHU-B23, B-4000 Liège-Sart Tilman, Belgium. vgeenen@ulg.ac.be
Louis
C
C
Martens
H
H
D000293:Adolescent; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D016207:Cytokines / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control; D006683:HLA-DQ Antigens / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008954:Models, Biological; D013950:Thymus Gland / Q000276:immunology*; D014611:Vaccination
D001324:Autoantigens; D016207:Cytokines; D006683:HLA-DQ Antigens; D007335:Insulin-Like Growth Factor II