2004
DOI: 10.1196/annals.1337.034
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Experimental Autoimmune Diabetes: A New Tool to Study Mechanisms and Consequences of Insulin‐Specific Autoimmunity

Abstract: (Prepro)insulin is considered a central antigenic determinant in diabetic autoimmunity. Insulin has been used to modify diabetes development in NOD mice and prediabetic individuals. We have recently shown that (prepro)insulin can adversely promote diabetes development in murine type 1 diabetes. Based on these findings we have developed experimental autoimmune diabetes (EAD), a new mouse model characterized by (1) CD4(+)/CD8(+) insulitis, induced by (2) (prepro)insulin DNA vaccination, leading to (3) beta cell … Show more

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Cited by 6 publications
(16 citation statements)
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“…B6 mice were immunized with pCI/preproinsulin N110A . Their splenic CD8 T-cells isolated 14 days after immunization were adoptively transferred into RIP-B7.1 mice (30). RIP-B7.1 hosts developed EAD after transfer with primed (Fig.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…B6 mice were immunized with pCI/preproinsulin N110A . Their splenic CD8 T-cells isolated 14 days after immunization were adoptively transferred into RIP-B7.1 mice (30). RIP-B7.1 hosts developed EAD after transfer with primed (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Expression of B7.1 in islet β-cells facilitated diabetes development by adoptively transferred preproinsulin-specific CD8 T-cells (Fig. 4 C ) (30). The RIP-B7.1 diabetes model is thus well suited to study distinct events in the priming and effector phase of preproinsulin-specific CD8 T-cells.…”
Section: Discussionmentioning
confidence: 99%
“…Genetic vaccines potently stimulate CD8 T cell responses [9]. We have shown that intramuscular DNA immunization with vectors encoding murine preproinsulin (ppins)-II efficiently induce de novo EAD in RIP-B7.1 mice and accelerate EAD development in NOD mice [10,11]. In this paper, we further characterized induction of EAD in RIP-B7.1 mice by ppins-specific DNA immunization.…”
Section: Introductionmentioning
confidence: 96%
“…DNA immunization induces Th1-biased immune responses to most Ags. In contrast, ballistic DNA immunization of low amounts (1-2 g/mouse) of plasmid DNA with the gene gun facilitated Th2-biased immunity (48) and failed to induce EAD in RIP-B7.1 mice even after repeated boost immunizations (data not shown) (49). We thus conclude that induction of autoreactive CD8 T cell responses requires costimulation of the Th1-biased immune system.…”
Section: Discussionmentioning
confidence: 63%
“…Alternatively, plasmid DNA-induced innate immune responses may directly facilitate ␤ cell susceptibility to T cell-mediated destruction (50). This is unlikely because K b /A 12-21 -monospecific CD8 T cells isolated from diabetic RIP-B7.1 mice immunized with pCI/L-A 12-21 DNA efficiently triggered EAD after adoptive cell transfer into RIP-B7.1 hosts (data not shown) (49). Thus, DNA immunization does not directly influence presentation of the K b /A 12-21 epitope by pancreatic ␤ cells.…”
Section: Discussionmentioning
confidence: 99%