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Fas ligand DNA enhances a vaccination effect by coadministered DNA encoding a tumor antigen through augmenting production of antibody against the tumor antigen.

Zhong B, Ma G, Sato A, Shimozato O, Liu H, Li Q, Shingyoji M, Tada Y, Tatsumi K, Shimada H, Hiroshima K, Tagawa M - J Immunol Res (2015)

Bottom Line: Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood.We did not detect increased numbers of β-gal-specific CD8(+) T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone.These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China ; Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.

ABSTRACT
Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood. We examined whether administration of DNA encoding FasL gene enhanced antitumor effects in mice that were vaccinated with DNA expressing a putative tumor antigen gene, β-galactosidase (β-gal). Growth of β-gal-positive Colon 26 tumors was retarded in the syngeneic mice immunized with β-gal and FasL DNA compared with those vaccinated with β-gal or FasL DNA. We did not detect increased numbers of β-gal-specific CD8(+) T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone. Subtype analysis of anti-β-gal antibody produced by the combination of β-gal and FasL DNA or β-gal DNA injection showed that IgG2a amounts were greater in mice injected with both DNA than those with β-gal DNA alone, but IgG2b amounts were lower in both DNA-injected than β-gal DNA-injected mice. These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

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Related in: MedlinePlus

Expression of β-gal protein in mice that received DNA immunization. BALB/c mice were injected with or without cardiotoxin at thigh muscles and then with pcDNA3/β-gal (10 or 50 μg) at the same muscles 5 days later. The thigh muscles were stained with the X-gal staining 5 days after DNA immunization.
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fig1: Expression of β-gal protein in mice that received DNA immunization. BALB/c mice were injected with or without cardiotoxin at thigh muscles and then with pcDNA3/β-gal (10 or 50 μg) at the same muscles 5 days later. The thigh muscles were stained with the X-gal staining 5 days after DNA immunization.

Mentions: We examined expression of the β-gal gene in muscles of mice that were injected with pcDNA3/β-gal plasmid DNA and investigated a possible enhancement of the gene expression with a cardiotoxin treatment (Figure 1). Cardiotoxin destroys muscle tissues and the regeneration process facilitates uptake of DNA [13, 14]. Expression levels of β-gal detected with the X-gal staining method depended on amounts of pcDNA3/β-gal DNA used, and the cardiotoxin treatment prior to DNA administration augmented the β-gal expression. We thereby treated mice with cardiotoxin and 5 days later immunized the mice with 50 μg DNA in the following experiments.


Fas ligand DNA enhances a vaccination effect by coadministered DNA encoding a tumor antigen through augmenting production of antibody against the tumor antigen.

Zhong B, Ma G, Sato A, Shimozato O, Liu H, Li Q, Shingyoji M, Tada Y, Tatsumi K, Shimada H, Hiroshima K, Tagawa M - J Immunol Res (2015)

Expression of β-gal protein in mice that received DNA immunization. BALB/c mice were injected with or without cardiotoxin at thigh muscles and then with pcDNA3/β-gal (10 or 50 μg) at the same muscles 5 days later. The thigh muscles were stained with the X-gal staining 5 days after DNA immunization.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352480&req=5

fig1: Expression of β-gal protein in mice that received DNA immunization. BALB/c mice were injected with or without cardiotoxin at thigh muscles and then with pcDNA3/β-gal (10 or 50 μg) at the same muscles 5 days later. The thigh muscles were stained with the X-gal staining 5 days after DNA immunization.
Mentions: We examined expression of the β-gal gene in muscles of mice that were injected with pcDNA3/β-gal plasmid DNA and investigated a possible enhancement of the gene expression with a cardiotoxin treatment (Figure 1). Cardiotoxin destroys muscle tissues and the regeneration process facilitates uptake of DNA [13, 14]. Expression levels of β-gal detected with the X-gal staining method depended on amounts of pcDNA3/β-gal DNA used, and the cardiotoxin treatment prior to DNA administration augmented the β-gal expression. We thereby treated mice with cardiotoxin and 5 days later immunized the mice with 50 μg DNA in the following experiments.

Bottom Line: Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood.We did not detect increased numbers of β-gal-specific CD8(+) T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone.These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China ; Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.

ABSTRACT
Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood. We examined whether administration of DNA encoding FasL gene enhanced antitumor effects in mice that were vaccinated with DNA expressing a putative tumor antigen gene, β-galactosidase (β-gal). Growth of β-gal-positive Colon 26 tumors was retarded in the syngeneic mice immunized with β-gal and FasL DNA compared with those vaccinated with β-gal or FasL DNA. We did not detect increased numbers of β-gal-specific CD8(+) T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone. Subtype analysis of anti-β-gal antibody produced by the combination of β-gal and FasL DNA or β-gal DNA injection showed that IgG2a amounts were greater in mice injected with both DNA than those with β-gal DNA alone, but IgG2b amounts were lower in both DNA-injected than β-gal DNA-injected mice. These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

Show MeSH
Related in: MedlinePlus