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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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Presentation of OVA and viral antigens by DCs from the draining mediastinal lymph nodes. B6 mice were infected with X-31 or mock infected on day 1. On day 2, 3, and 4, they were administered egg OVA. On day 4, CD11c+ and CD11c− cells were purified from the draining LNs (six mice/group) and cocultured with OT-I cells for 48–72 h and assessed for T cell proliferation by 3H-thymidine incorporation. (A) Proliferation of OT-I T cells in the presence of CD11c+ or CD11c− lymph node presenting cells purified from draining mediastinal lymph nodes and nondraining brachial lymph nodes. (B) Proliferation of bulk influenza virus-specific T cells in the presence of CD11c+ and CD11c− cells enriched from the draining lymph nodes in part A.
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fig4: Presentation of OVA and viral antigens by DCs from the draining mediastinal lymph nodes. B6 mice were infected with X-31 or mock infected on day 1. On day 2, 3, and 4, they were administered egg OVA. On day 4, CD11c+ and CD11c− cells were purified from the draining LNs (six mice/group) and cocultured with OT-I cells for 48–72 h and assessed for T cell proliferation by 3H-thymidine incorporation. (A) Proliferation of OT-I T cells in the presence of CD11c+ or CD11c− lymph node presenting cells purified from draining mediastinal lymph nodes and nondraining brachial lymph nodes. (B) Proliferation of bulk influenza virus-specific T cells in the presence of CD11c+ and CD11c− cells enriched from the draining lymph nodes in part A.

Mentions: To define the cell types involved in the presentation of OVA in the draining lymph nodes, we purified CD11c+ and CD11c− cells and added these to cultures of OVA-specific transgenic T cells to stimulate proliferation. Again, the mice received either aerosolized influenza virus or mock infection, followed by aerosolized egg OVA for three consecutive days. 1 d after the last OVA treatment, the antigen-presenting cells were purified from draining mediastinal lymph nodes and nondraining brachial lymph nodes and tested (Fig. 4). Only CD11c+ cells from the mediastinal lymph nodes could elicit OT-I T cell proliferation, indicating that DCs were the major cell involved in the presentation of OVA in the draining lymph nodes. CD11c+ cells from mice infected with influenza virus and egg OVA were much more efficient at presenting OVA to OT-I (and OT-II cells, unpublished data) than CD11c+ cells from mice receiving egg OVA only (Fig. 4 A), but the later did stimulate above the PBS background control. The DCs from influenza virus infected mice also stimulated influenza primed T cells (Fig. 4 B), demonstrating that DCs as a population are capable of both presenting OVA peptides and influenza virus peptides.


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)

Presentation of OVA and viral antigens by DCs from the draining mediastinal lymph nodes. B6 mice were infected with X-31 or mock infected on day 1. On day 2, 3, and 4, they were administered egg OVA. On day 4, CD11c+ and CD11c− cells were purified from the draining LNs (six mice/group) and cocultured with OT-I cells for 48–72 h and assessed for T cell proliferation by 3H-thymidine incorporation. (A) Proliferation of OT-I T cells in the presence of CD11c+ or CD11c− lymph node presenting cells purified from draining mediastinal lymph nodes and nondraining brachial lymph nodes. (B) Proliferation of bulk influenza virus-specific T cells in the presence of CD11c+ and CD11c− cells enriched from the draining lymph nodes in part A.
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Related In: Results  -  Collection

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

fig4: Presentation of OVA and viral antigens by DCs from the draining mediastinal lymph nodes. B6 mice were infected with X-31 or mock infected on day 1. On day 2, 3, and 4, they were administered egg OVA. On day 4, CD11c+ and CD11c− cells were purified from the draining LNs (six mice/group) and cocultured with OT-I cells for 48–72 h and assessed for T cell proliferation by 3H-thymidine incorporation. (A) Proliferation of OT-I T cells in the presence of CD11c+ or CD11c− lymph node presenting cells purified from draining mediastinal lymph nodes and nondraining brachial lymph nodes. (B) Proliferation of bulk influenza virus-specific T cells in the presence of CD11c+ and CD11c− cells enriched from the draining lymph nodes in part A.
Mentions: To define the cell types involved in the presentation of OVA in the draining lymph nodes, we purified CD11c+ and CD11c− cells and added these to cultures of OVA-specific transgenic T cells to stimulate proliferation. Again, the mice received either aerosolized influenza virus or mock infection, followed by aerosolized egg OVA for three consecutive days. 1 d after the last OVA treatment, the antigen-presenting cells were purified from draining mediastinal lymph nodes and nondraining brachial lymph nodes and tested (Fig. 4). Only CD11c+ cells from the mediastinal lymph nodes could elicit OT-I T cell proliferation, indicating that DCs were the major cell involved in the presentation of OVA in the draining lymph nodes. CD11c+ cells from mice infected with influenza virus and egg OVA were much more efficient at presenting OVA to OT-I (and OT-II cells, unpublished data) than CD11c+ cells from mice receiving egg OVA only (Fig. 4 A), but the later did stimulate above the PBS background control. The DCs from influenza virus infected mice also stimulated influenza primed T cells (Fig. 4 B), demonstrating that DCs as a population are capable of both presenting OVA peptides and influenza virus peptides.

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