Priming Protective CD8 T Cell Immunity by DNA Vaccines Encoding Chimeric, Stress Protein-Capturing Tumor-Associated Antigen

Schirmbeck, Reinhold; Riedl, Petra; Kupferschmitt, Mark; Wegenka, Ursula; Hauser, Hansjörg; Rice, Jason; Kröger, Andrea; Reimann, Jörg

doi:10.4049/jimmunol.177.3.1534

Cited by 15 publications

(18 citation statements)

References 52 publications

(54 reference statements)

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“…The HA-tagged intermediates that could be expressed from the pCI/ppins-HA construct are: the 14.5-kD ppins-HA, the 11.5-kD pins-HA and the 3.5-kD A-HA. HEK293 cells were transiently transfected with pCI/ppins-HA and immunoprecipitated with HA-specific mAb [12]. SDS-PAGE analysis revealed only the 11.5-kD pins-HA band ( Fig.…”

Section: Characterization Of Ppins Expression In Non-pancreatic Cellsmentioning

confidence: 99%

“…In response to immunization with the pCI/ppins DNA, an infiltration of CD4 and CD8 T cells appeared early in pancreatic islets. To determine which T cell subset(s) are required to prime the diabetogenic response, we eliminated CD4 T cells or CD8 T cells by treatment with depleting antibodies before and following DNA vaccination [12]. Depletion efficacy of T cell subsets (monitored in peripheral blood) was >95% 5 days after the last injection [12].…”

Section: Cd4 and Cd8 T Cell Infiltration Into Pancreatic Islets Precementioning

confidence: 99%

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The diabetogenic, insulin‐specific CD8 T cell response primed in the experimental autoimmune diabetes model in RIP‐B7.1 mice

et al. 2007

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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 hu-ppins. EAD induction critically depends on CD8 T cells and is independent of CD4 T cells. To be diabetogenic, ppins-specific CD8 T cells had to express IFN-c. Neither expression of perforin nor signaling through the type I IFN receptor is an essential component of this pathogenic CD8 T cell phenotype. Using plasmids encoding truncated ppins variants, we show that EAD is only induced by DNA vaccines encoding the insulin A-chain. Diabetogenic CD8 T cells specifically recognize the K b -restricted A 12-21 epitope of the insulin A-chain. The RIP-B7.1 model hence represents an attractive model for the characterization of cellular and molecular events involved in the CD8 T cell-mediated immune pathogenesis of diabetes.

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Section: Characterization Of Ppins Expression In Non-pancreatic Cellsmentioning

confidence: 99%

Section: Cd4 and Cd8 T Cell Infiltration Into Pancreatic Islets Precementioning

confidence: 99%

The diabetogenic, insulin‐specific CD8 T cell response primed in the experimental autoimmune diabetes model in RIP‐B7.1 mice

et al. 2007

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“…80,81 There are several examples of cancer associated with increased frequencies of Tregs in circulation or in the tumor tissues. 82,83 Tumor-infiltrating DCs and macrophages monocytogenes, 46 as well as tumor antigens 47 providing CTLmediated tumor protection in different cancer models. CTLs can specifically eliminate malignantly transformed cells expressing tumor antigens without affecting other tissues.…”

Section: Tumor-associated Tolerance and Immunosuppressionmentioning

confidence: 99%

Harnessing DNA-induced immune responses for improving cancer vaccines

Herrada

Rojas-Colonelli

González-Figueroa

et al. 2012

Human Vaccines & Immunotherapeutics

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“…Multiple mouse tumor lines express GP70, a product of the env gene of endogenous Murine Leukemia Virus (MuLV) (16–18). CD8+ T cell responses against the AH1 epitope, GP70 423–431 , protect against tumor challenge with the CT26 tumor cell line (5, 6, 17, 18).…”

Section: Introductionmentioning

confidence: 99%

“…CD8+ T cell responses against the AH1 epitope, GP70 423–431 , protect against tumor challenge with the CT26 tumor cell line (5, 6, 17, 18). Work by our group and others has shown that expression of this antigen in normal tissues induces tolerance in the T cell repertoire (18, 19). Subsequently, vaccination with the AH1 epitope alone is poorly immunogenic (5, 7).…”

Section: Introductionmentioning

confidence: 99%

Elevated Tumor-Associated Antigen Expression Suppresses Variant Peptide Vaccine Responses

Kemmler

Clambey

Kedl

et al. 2011

The Journal of Immunology

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Variant peptide vaccines are used clinically to expand T cells that cross-react with tumor-associated antigens (TAA). To investigate the effects of elevated endogenous TAA expression on variant peptide-induced responses, we used the GP70 TAA model. Although young BALB/c mice display T cell tolerance to the TAA GP70423–431 (AH1), expression of GP70 and suppression of AH1-specific responses increases with age. We hypothesized that as TAA expression increases, the AH1-crossreactivity of variant peptide-elicited T cell responses diminishes. Controlling for immunosenescence, we showed that elevated GP70 expression suppressed AH1-crossreactive responses elicited by two AH1 peptide variants. A variant that elicited almost exclusively AH1-crossreactive T cells in young mice elicited few or no T cells in aging mice with antibody-detectable GP70 expression. In contrast, a variant that elicited a less AH1-crossreactive T cell response in young mice successfully expanded AH1-crossreactive T cells in all aging mice tested. However, these T cells bound the AH1/MHC complex with a relatively short half-life and responded poorly to ex vivo stimulation with the AH1 peptide. Variant peptide vaccine responses were also suppressed when AH1 peptide is administered tolerogenically to young mice prior to vaccination. Analyses of variant-specific precursor T cells from naïve mice with antibody-detectable GP70 expression determined that these T cells expressed PD-1 and had downregulated IL-7Rα expression, suggesting they were anergic or undergoing deletion. Although variant peptide vaccines were less effective as TAA expression increases, data presented here also suggest that complementary immunotherapies may induce the expansion of T cells with functional TAA recognition.

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Priming Protective CD8 T Cell Immunity by DNA Vaccines Encoding Chimeric, Stress Protein-Capturing Tumor-Associated Antigen

Cited by 15 publications

References 52 publications

The diabetogenic, insulin‐specific CD8 T cell response primed in the experimental autoimmune diabetes model in RIP‐B7.1 mice

The diabetogenic, insulin‐specific CD8 T cell response primed in the experimental autoimmune diabetes model in RIP‐B7.1 mice

Harnessing DNA-induced immune responses for improving cancer vaccines

Elevated Tumor-Associated Antigen Expression Suppresses Variant Peptide Vaccine Responses

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