2007
DOI: 10.1002/eji.200737222
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The diabetogenic, insulin‐specific CD8 T cell response primed in the experimental autoimmune diabetes model in RIP‐B7.1 mice

Abstract: Type 1 diabetes mellitus can result from the specific destruction of pancreatic beta cells by autoreactive T cells. As shown here, experimental autoimmune diabetes (EAD) is efficiently induced in RIP-B7.1 mice by preproinsulin (ppins)-encoding DNA vaccines. EAD develops in RIP-B7.1 mice within 3-4 wk after a single immunization with ppinsencoding plasmid DNA. RIP-B7.1 mice develop insulitis, insulin deficiency and hyperglycemia after vaccination with plasmids encoding murine ppins-I or murine ppins-II or human… Show more

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Cited by 15 publications
(36 citation statements)
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References 23 publications
(54 reference statements)
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“…Also, in mouse models of experimental diabetes, except for those where foreign antigens are expressed from the rat insulin promoter, most described CD8 T cell targets are peptides that bind MHC-I molecules with low affinity (29) (30). The low affinity of the diabetogenic epitope IGRP 5′UTR [7][8][9][10][11][12][13][14] , targeted in our model (Figure 4), further supports this notion.…”
Section: Discussionsupporting
confidence: 73%
“…Also, in mouse models of experimental diabetes, except for those where foreign antigens are expressed from the rat insulin promoter, most described CD8 T cell targets are peptides that bind MHC-I molecules with low affinity (29) (30). The low affinity of the diabetogenic epitope IGRP 5′UTR [7][8][9][10][11][12][13][14] , targeted in our model (Figure 4), further supports this notion.…”
Section: Discussionsupporting
confidence: 73%
“…Destruction of pancreatic ␤ cells depended on IFN-␥-producing, ppins-specific CD8 T cells (15). We previously showed that RIP-B7.1 mice deficient in IFN-␥ could not induce EAD after immunization with pCI/ppins DNA (15). It has been suggested that IFN-␥ may directly mediate ␤ cell destruction and/or facilitate MHC class I-restricted presentation of the diabetogenic epitope(s) to CD8 T cells (16 -18).…”
Section: T Ype 1 Diabetes Mellitus (T1d)mentioning
confidence: 98%
“…We used RIP-B7.1 mice (11) that express the costimulator molecule B7.1 (CD80) on pancreatic ␤ cells to characterize the specificity and diabetogenic potential of CD8 T cell responses (12)(13)(14)(15). Studies have shown that DNA vectors encoding murine preproinsulin-II (ppins) efficiently induced CD8 T cell-dependent experimental autoimmune diabetes (EAD) in RIP-B7.1 (but not B6) mice within 3-4 wk after immunization (15). The EAD was characterized by insulitis, progressive invasion of T cells into the islets, ␤ cell destruction, and hyperglycemia (15).…”
Section: T Ype 1 Diabetes Mellitus (T1d)mentioning
confidence: 99%
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