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Influenza virus-induced dendritic cell maturation is associated with the induction of strong T cell immunity to a coadministered, normally nonimmunogenic protein.

Brimnes MK, Bonifaz L, Steinman RM, Moran TM - J. Exp. Med. (2003)

Bottom Line: In its absence, OVA failed to induce B and T cell responses and even tolerized, but with influenza, OVA-specific antibodies and CD8+ cytolytic T lymphocytes developed.The relatively slow (2-3 d) kinetics of maturation correlated closely to the time at which OVA inhalation elicited specific antibodies.Therefore respiratory infection can induce DC maturation and simultaneously B and T cell immunity to an innocuous antigen inhaled concurrently.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, 10029 NY, USA.

ABSTRACT
We evaluated the proposal that during microbial infection, dendritic cells (DCs) undergo maturation and present a mixture of peptides derived from the microbe as well as harmless environmental antigens. Mice were exposed to an aerosol of endotoxin free ovalbumin (OVA) in the absence or presence of influenza virus. In its absence, OVA failed to induce B and T cell responses and even tolerized, but with influenza, OVA-specific antibodies and CD8+ cytolytic T lymphocytes developed. With or without infection, OVA was presented selectively in the draining mediastinal lymph nodes, as assessed by the comparable proliferation of infused, CD8+ and CD4+, TCR transgenic T cells. In the absence of influenza, these OVA-specific T cells produced little IL-2, IL-4, IL-10, and IFN-gamma, but with infection, both CD4+ and CD8+ T cells made high levels of IL-2 and IFN-gamma. The OVA plus influenza-treated mice also showed accelerated recovery to a challenge with recombinant vaccinia OVA virus. CD11c+ DCs from the mediastinal lymph nodes of infected mice selectively stimulated both OVA- and influenza-specific T cells and underwent maturation, with higher levels of MHC class II, CD80, and CD86 molecules. The relatively slow (2-3 d) kinetics of maturation correlated closely to the time at which OVA inhalation elicited specific antibodies. Therefore respiratory infection can induce DC maturation and simultaneously B and T cell immunity to an innocuous antigen inhaled concurrently.

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Influenza virus induced DCs maturation correlates with production of OVA-specific antibodies. (A) Six B6 mice/group were infected with X-31 or mock infected and CD11c+ cells were purified from the draining LNs 20, 45 and 72 h after infection and stained for expression of CD80, CD86, and MHC II. (B) Four mice/group were infected with X-31 at time point 0. At various time points post virus infection (0, 20, 45, 72, 96 h, 7 d, and 10 d), the mice received a single dose of egg OVA. 22 d after virus infection, the serum was analyzed for OVA-specific IgG1 and IgG2b antibodies. All the black bars are significantly different from the white bars (P < 0.05) except for day 7 in the IgG1 chart. Data are expressed as mean ± SD and shown at 1:10 serum dilutions. Data are representative of three experiments.
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fig6: Influenza virus induced DCs maturation correlates with production of OVA-specific antibodies. (A) Six B6 mice/group were infected with X-31 or mock infected and CD11c+ cells were purified from the draining LNs 20, 45 and 72 h after infection and stained for expression of CD80, CD86, and MHC II. (B) Four mice/group were infected with X-31 at time point 0. At various time points post virus infection (0, 20, 45, 72, 96 h, 7 d, and 10 d), the mice received a single dose of egg OVA. 22 d after virus infection, the serum was analyzed for OVA-specific IgG1 and IgG2b antibodies. All the black bars are significantly different from the white bars (P < 0.05) except for day 7 in the IgG1 chart. Data are expressed as mean ± SD and shown at 1:10 serum dilutions. Data are representative of three experiments.

Mentions: To test if the maturation status of the DCs was correlated with the priming of OVA-specific immunity, we first assessed maturation at several time points after influenza virus infection. 20 h after infection, we did not observe any differences in the levels of costimulatory molecules (CD80 and CD86) and MHC II between influenza virus and mock-infected mice. However, by 45 h we detected an up-regulation of CD80, CD86, and MHC II in mice infected with influenza virus, and this effect was maximal at 72 h (Fig. 6 A). At 96 h, the expression of maturation markers was slightly reduced compared with the 72 h time point. At day 7, we observed a down-regulation of maturation markers compared with the mock-infected mice, and this down-regulation was even more pronounced at day 10 (unpublished data). At the same time points during the course of influenza infection (0, 20, 45, 72, 96 h, 7 d, 10 d), we aerosolized a single dose of egg OVA and evaluated the OVA-specific antibody response as a read-out for immune priming. As shown in Fig. 6 B, the production of OVA-specific antibodies correlated with the degree of maturation of the DCs. The best responses were obtained when the maturation of the DCs was peaking, whereas negligible OVA-specific antibody responses were induced when OVA was given at 0, 20 h, or days 7 and 10. These results indicate that the maturation of DCs in vivo correlates well with the induction of immune responses.


Influenza virus-induced dendritic cell maturation is associated with the induction of strong T cell immunity to a coadministered, normally nonimmunogenic protein.

Brimnes MK, Bonifaz L, Steinman RM, Moran TM - J. Exp. Med. (2003)

Influenza virus induced DCs maturation correlates with production of OVA-specific antibodies. (A) Six B6 mice/group were infected with X-31 or mock infected and CD11c+ cells were purified from the draining LNs 20, 45 and 72 h after infection and stained for expression of CD80, CD86, and MHC II. (B) Four mice/group were infected with X-31 at time point 0. At various time points post virus infection (0, 20, 45, 72, 96 h, 7 d, and 10 d), the mice received a single dose of egg OVA. 22 d after virus infection, the serum was analyzed for OVA-specific IgG1 and IgG2b antibodies. All the black bars are significantly different from the white bars (P < 0.05) except for day 7 in the IgG1 chart. Data are expressed as mean ± SD and shown at 1:10 serum dilutions. Data are representative of three experiments.
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Related In: Results  -  Collection

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fig6: Influenza virus induced DCs maturation correlates with production of OVA-specific antibodies. (A) Six B6 mice/group were infected with X-31 or mock infected and CD11c+ cells were purified from the draining LNs 20, 45 and 72 h after infection and stained for expression of CD80, CD86, and MHC II. (B) Four mice/group were infected with X-31 at time point 0. At various time points post virus infection (0, 20, 45, 72, 96 h, 7 d, and 10 d), the mice received a single dose of egg OVA. 22 d after virus infection, the serum was analyzed for OVA-specific IgG1 and IgG2b antibodies. All the black bars are significantly different from the white bars (P < 0.05) except for day 7 in the IgG1 chart. Data are expressed as mean ± SD and shown at 1:10 serum dilutions. Data are representative of three experiments.
Mentions: To test if the maturation status of the DCs was correlated with the priming of OVA-specific immunity, we first assessed maturation at several time points after influenza virus infection. 20 h after infection, we did not observe any differences in the levels of costimulatory molecules (CD80 and CD86) and MHC II between influenza virus and mock-infected mice. However, by 45 h we detected an up-regulation of CD80, CD86, and MHC II in mice infected with influenza virus, and this effect was maximal at 72 h (Fig. 6 A). At 96 h, the expression of maturation markers was slightly reduced compared with the 72 h time point. At day 7, we observed a down-regulation of maturation markers compared with the mock-infected mice, and this down-regulation was even more pronounced at day 10 (unpublished data). At the same time points during the course of influenza infection (0, 20, 45, 72, 96 h, 7 d, 10 d), we aerosolized a single dose of egg OVA and evaluated the OVA-specific antibody response as a read-out for immune priming. As shown in Fig. 6 B, the production of OVA-specific antibodies correlated with the degree of maturation of the DCs. The best responses were obtained when the maturation of the DCs was peaking, whereas negligible OVA-specific antibody responses were induced when OVA was given at 0, 20 h, or days 7 and 10. These results indicate that the maturation of DCs in vivo correlates well with the induction of immune responses.

Bottom Line: In its absence, OVA failed to induce B and T cell responses and even tolerized, but with influenza, OVA-specific antibodies and CD8+ cytolytic T lymphocytes developed.The relatively slow (2-3 d) kinetics of maturation correlated closely to the time at which OVA inhalation elicited specific antibodies.Therefore respiratory infection can induce DC maturation and simultaneously B and T cell immunity to an innocuous antigen inhaled concurrently.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, 10029 NY, USA.

ABSTRACT
We evaluated the proposal that during microbial infection, dendritic cells (DCs) undergo maturation and present a mixture of peptides derived from the microbe as well as harmless environmental antigens. Mice were exposed to an aerosol of endotoxin free ovalbumin (OVA) in the absence or presence of influenza virus. In its absence, OVA failed to induce B and T cell responses and even tolerized, but with influenza, OVA-specific antibodies and CD8+ cytolytic T lymphocytes developed. With or without infection, OVA was presented selectively in the draining mediastinal lymph nodes, as assessed by the comparable proliferation of infused, CD8+ and CD4+, TCR transgenic T cells. In the absence of influenza, these OVA-specific T cells produced little IL-2, IL-4, IL-10, and IFN-gamma, but with infection, both CD4+ and CD8+ T cells made high levels of IL-2 and IFN-gamma. The OVA plus influenza-treated mice also showed accelerated recovery to a challenge with recombinant vaccinia OVA virus. CD11c+ DCs from the mediastinal lymph nodes of infected mice selectively stimulated both OVA- and influenza-specific T cells and underwent maturation, with higher levels of MHC class II, CD80, and CD86 molecules. The relatively slow (2-3 d) kinetics of maturation correlated closely to the time at which OVA inhalation elicited specific antibodies. Therefore respiratory infection can induce DC maturation and simultaneously B and T cell immunity to an innocuous antigen inhaled concurrently.

Show MeSH
Related in: MedlinePlus