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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 induces maturation of DCs from the draining mediastinal lymph nodes. Six B6 mice/group were administered X-31, PBS, or egg OVA at time point 0. The egg OVA group received OVA at 24 and 48 h also. 72 h after infection CD11c+ and CD11c− cells were purified from the draining lymph nodes and stained for expression of CD80, CD86, MHC II, B220, CD11b, and F4/80. (A) The DC population is gated on CD11c+ cells, (B) the B cell population is gated on B220+ cells and (C and D) the macrophages are gated as CD11c−, CD11b+, and F4/80+ or F4/80− (arrows to the two macrophage subsets). Data are representative of at least two experiments.
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fig5: Influenza virus induces maturation of DCs from the draining mediastinal lymph nodes. Six B6 mice/group were administered X-31, PBS, or egg OVA at time point 0. The egg OVA group received OVA at 24 and 48 h also. 72 h after infection CD11c+ and CD11c− cells were purified from the draining lymph nodes and stained for expression of CD80, CD86, MHC II, B220, CD11b, and F4/80. (A) The DC population is gated on CD11c+ cells, (B) the B cell population is gated on B220+ cells and (C and D) the macrophages are gated as CD11c−, CD11b+, and F4/80+ or F4/80− (arrows to the two macrophage subsets). Data are representative of at least two experiments.

Mentions: Because influenza infection was associated with an immune response to coadministered OVA, we looked for the development of mature DCs in the mediastinal lymph nodes, using changes in cell surface phenotype as a criterion. Mice inhaled aerosolized OVA or influenza, and then we evaluated the expression of maturation markers on CD11c+ and CD11c− cells 72 h later. The expression of CD80, CD86, and MHC II were each up-regulated on CD11c+ cells from influenza virus–infected animals, when compared with cells from mice that were mock infected or received egg OVA only (Fig. 5). As Akbari et al. (9) recently described the induction of ICOS-L as well as CD80 and CD86 after intranasal OVA, we also checked for expression of ICOS-L on mediastinal lymph node DCs 3 d after inhalation of LPS-free OVA. While CD80 and CD86 expression increased markedly after influenza virus infection, ICOS-L was only slightly up-regulated and only in the presence of influenza virus (unpublished data). The influenza virus infection also had an impact on the number of CD11c+ cells in the draining lymph nodes, because the frequency of CD11c+ cells and the total number of mediastinal lymph node cells were each increased up to twofold compared with mock infected mice or mice administered egg OVA. Influenza infection also was accompanied by an expansion of CD11c− CD11b+ macrophages expressing or not expressing the F4/80 antigen (Fig. 5 C, arrows), but in contrast to DCs, B cells and macrophages did not show increased expression of CD80/86 (Figs. 5, B and D). Overall these results demonstrate that influenza virus leads to DC maturation without inducing T cell costimulatory molecules on B cells and macrophages.


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 induces maturation of DCs from the draining mediastinal lymph nodes. Six B6 mice/group were administered X-31, PBS, or egg OVA at time point 0. The egg OVA group received OVA at 24 and 48 h also. 72 h after infection CD11c+ and CD11c− cells were purified from the draining lymph nodes and stained for expression of CD80, CD86, MHC II, B220, CD11b, and F4/80. (A) The DC population is gated on CD11c+ cells, (B) the B cell population is gated on B220+ cells and (C and D) the macrophages are gated as CD11c−, CD11b+, and F4/80+ or F4/80− (arrows to the two macrophage subsets). Data are representative of at least two experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196079&req=5

fig5: Influenza virus induces maturation of DCs from the draining mediastinal lymph nodes. Six B6 mice/group were administered X-31, PBS, or egg OVA at time point 0. The egg OVA group received OVA at 24 and 48 h also. 72 h after infection CD11c+ and CD11c− cells were purified from the draining lymph nodes and stained for expression of CD80, CD86, MHC II, B220, CD11b, and F4/80. (A) The DC population is gated on CD11c+ cells, (B) the B cell population is gated on B220+ cells and (C and D) the macrophages are gated as CD11c−, CD11b+, and F4/80+ or F4/80− (arrows to the two macrophage subsets). Data are representative of at least two experiments.
Mentions: Because influenza infection was associated with an immune response to coadministered OVA, we looked for the development of mature DCs in the mediastinal lymph nodes, using changes in cell surface phenotype as a criterion. Mice inhaled aerosolized OVA or influenza, and then we evaluated the expression of maturation markers on CD11c+ and CD11c− cells 72 h later. The expression of CD80, CD86, and MHC II were each up-regulated on CD11c+ cells from influenza virus–infected animals, when compared with cells from mice that were mock infected or received egg OVA only (Fig. 5). As Akbari et al. (9) recently described the induction of ICOS-L as well as CD80 and CD86 after intranasal OVA, we also checked for expression of ICOS-L on mediastinal lymph node DCs 3 d after inhalation of LPS-free OVA. While CD80 and CD86 expression increased markedly after influenza virus infection, ICOS-L was only slightly up-regulated and only in the presence of influenza virus (unpublished data). The influenza virus infection also had an impact on the number of CD11c+ cells in the draining lymph nodes, because the frequency of CD11c+ cells and the total number of mediastinal lymph node cells were each increased up to twofold compared with mock infected mice or mice administered egg OVA. Influenza infection also was accompanied by an expansion of CD11c− CD11b+ macrophages expressing or not expressing the F4/80 antigen (Fig. 5 C, arrows), but in contrast to DCs, B cells and macrophages did not show increased expression of CD80/86 (Figs. 5, B and D). Overall these results demonstrate that influenza virus leads to DC maturation without inducing T cell costimulatory molecules on B cells and macrophages.

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