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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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Production of ant-β-gal Ab after DNA immunization. BALB/c mice were treated with cardiotoxin followed by DNA immunization, pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL, pcDNA3/β-gal + pCAGGS, or pcDNA3/β-gal + pCAGGS/FasL (50 μg DNA for each). (a) Concentrations of anti-β-gal IgG Ab in the mice 14 days after DNA immunization were measured with an ELISA assay (n = 3). (b) Concentrations of Ig subclasses were expressed as an optical density value (n = 3). #P < 0.05, *P < 0.01.
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fig4: Production of ant-β-gal Ab after DNA immunization. BALB/c mice were treated with cardiotoxin followed by DNA immunization, pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL, pcDNA3/β-gal + pCAGGS, or pcDNA3/β-gal + pCAGGS/FasL (50 μg DNA for each). (a) Concentrations of anti-β-gal IgG Ab in the mice 14 days after DNA immunization were measured with an ELISA assay (n = 3). (b) Concentrations of Ig subclasses were expressed as an optical density value (n = 3). #P < 0.05, *P < 0.01.

Mentions: We examined a possible involvement of humoral immunity in the antitumor effects by the immunization of β-gal and FasL DNA. We firstly measured serum concentrations of anti-β-gal IgG Ab produced by DNA immunization (Figure 4(a)). Injection of β-gal DNA increased anti-β-gal Ab as demonstrated between the group injected with pcDNA3/β-gal + pCAGGS DNA and that with pcDNA3 + pCAGGS DNA (P < 0.05), whereas injection of FasL DNA did not (pcDNA3 + pCAGGS/FasL versus pcDNA3 + pCAGGS, P = 0.48). Coinjected FasL DNA together with β-gal DNA however augmented the Ab production since the group injected with pcDNA3/β-gal + pCAGGS/FasL DNA showed greater responses than that with pcDNA3 + pCAGGS/FasL or pcDNA3/β-gal + pCAGGS DNA (P < 0.01). We then further examined a possible influence of FasL DNA injection on differential Ig isotype production (Figure 4(b)). IgG2a amounts were greater in immunization with both β-gal and FasL DNA than in that with β-gal DNA alone (P < 0.01), whereas IgG2b amounts were rather less in the injection of β-gal plus FasL DNA than in that of β-gal DNA alone (P < 0.01). The amounts of IgM and IgG1 were not different between the mice injected with both β-gal and FasL DNA and those with β-gal DNA (IgM; P = 0.29, IgG1; P = 0.85).


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)

Production of ant-β-gal Ab after DNA immunization. BALB/c mice were treated with cardiotoxin followed by DNA immunization, pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL, pcDNA3/β-gal + pCAGGS, or pcDNA3/β-gal + pCAGGS/FasL (50 μg DNA for each). (a) Concentrations of anti-β-gal IgG Ab in the mice 14 days after DNA immunization were measured with an ELISA assay (n = 3). (b) Concentrations of Ig subclasses were expressed as an optical density value (n = 3). #P < 0.05, *P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4352480&req=5

fig4: Production of ant-β-gal Ab after DNA immunization. BALB/c mice were treated with cardiotoxin followed by DNA immunization, pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL, pcDNA3/β-gal + pCAGGS, or pcDNA3/β-gal + pCAGGS/FasL (50 μg DNA for each). (a) Concentrations of anti-β-gal IgG Ab in the mice 14 days after DNA immunization were measured with an ELISA assay (n = 3). (b) Concentrations of Ig subclasses were expressed as an optical density value (n = 3). #P < 0.05, *P < 0.01.
Mentions: We examined a possible involvement of humoral immunity in the antitumor effects by the immunization of β-gal and FasL DNA. We firstly measured serum concentrations of anti-β-gal IgG Ab produced by DNA immunization (Figure 4(a)). Injection of β-gal DNA increased anti-β-gal Ab as demonstrated between the group injected with pcDNA3/β-gal + pCAGGS DNA and that with pcDNA3 + pCAGGS DNA (P < 0.05), whereas injection of FasL DNA did not (pcDNA3 + pCAGGS/FasL versus pcDNA3 + pCAGGS, P = 0.48). Coinjected FasL DNA together with β-gal DNA however augmented the Ab production since the group injected with pcDNA3/β-gal + pCAGGS/FasL DNA showed greater responses than that with pcDNA3 + pCAGGS/FasL or pcDNA3/β-gal + pCAGGS DNA (P < 0.01). We then further examined a possible influence of FasL DNA injection on differential Ig isotype production (Figure 4(b)). IgG2a amounts were greater in immunization with both β-gal and FasL DNA than in that with β-gal DNA alone (P < 0.01), whereas IgG2b amounts were rather less in the injection of β-gal plus FasL DNA than in that of β-gal DNA alone (P < 0.01). The amounts of IgM and IgG1 were not different between the mice injected with both β-gal and FasL DNA and those with β-gal DNA (IgM; P = 0.29, IgG1; P = 0.85).

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