2000
DOI: 10.4049/jimmunol.165.12.6748
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Early Th1 Response in Unprimed Nonobese Diabetic Mice to the Tyrosine Phosphatase-Like Insulinoma-Associated Protein 2, an Autoantigen in Type 1 Diabetes

Abstract: The insulinoma-associated protein 2 (IA-2) is a phosphatase-like autoantigen inducing T and B cell responses associated with human insulin-dependent diabetes mellitus (IDDM). We now report that T cell responses to IA-2 can also be detected in the nonobese diabetic (NOD) mouse, a model of human IDDM. Cytokine secretion in response to purified mouse rIA-2, characterized by high IFN-γ and relatively low IL-10 and IL-6 secretion, was elicited in spleen cells from unprimed NOD mice. Conversely, no response to IA-2 … Show more

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Cited by 34 publications
(52 citation statements)
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“…This would result in a net increase of IL-12 activity, consistent with the enhanced development of Th1 responses seen in NOD compared to other mouse strains. 25 There appears to be allele-specific regulation of IL12B expression in humans, but there are no common IL-12p40 isoforms. 10,11 As shown here for the mouse, there appears to be similar allele-specific control of Il12b expression, which may show further allele-specific biological affects of IL-12 due to changes at the protein level.…”
Section: Discussionmentioning
confidence: 99%
“…This would result in a net increase of IL-12 activity, consistent with the enhanced development of Th1 responses seen in NOD compared to other mouse strains. 25 There appears to be allele-specific regulation of IL12B expression in humans, but there are no common IL-12p40 isoforms. 10,11 As shown here for the mouse, there appears to be similar allele-specific control of Il12b expression, which may show further allele-specific biological affects of IL-12 due to changes at the protein level.…”
Section: Discussionmentioning
confidence: 99%
“…Some of the most studied ␤ cell Ags that can effectively inhibit the long-term development of T1DM in NOD mice (when administered in IFA) include; insulin ␤-chain (34, 39), HSPp277 (33), whole GAD (40), GAD(217-236) (29), GAD(524 -543) (29), and GAD(78 -97) (our unpublished observations). We treated female NOD mice neonatally with one of these ␤ cell autoantigens, or a control Ag, in IFA and tested their responses to the panel of Ags at 28 days of age, a time at which spontaneous autoimmunity is just beginning to become detectable to a limited number of ␤ cell Ags in unmanipulated NOD mice (2,8,14,41). By treating the mice and testing their autoimmune responses at an early age, we avoided confounding the results with the many spontaneous autoimmune responses that naturally arise at later stages of the disease process, thereby allowing us to readily discern any neoautoimmunity induced by the immunotherapy.…”
Section: The Administration Of Non-␤-cell Ags Induces Th2-polarized Rmentioning
confidence: 99%
“…16). An immunogenic hen egg lysozyme (HEL) peptide HEL [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] (AMKRHGLD NYRGYSL; Ref. 17) was used as a control foreign peptide and a mouse serum albumin (MSA) peptide MSA 560 -574 (KPKATAEQLKTVMDD; Ref.…”
Section: Antigensmentioning
confidence: 99%