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Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity  Colin de Haar, PhD, Mirjam Kool, BSc, Ine.

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Presentation on theme: "Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity  Colin de Haar, PhD, Mirjam Kool, BSc, Ine."— Presentation transcript:

1 Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity  Colin de Haar, PhD, Mirjam Kool, BSc, Ine Hassing, BSc, Marianne Bol, BSc, Bart N. Lambrecht, MD, PhD, Raymond Pieters, PhD  Journal of Allergy and Clinical Immunology  Volume 121, Issue 5, Pages (May 2008) DOI: /j.jaci Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Electron micrograph of ultrafine CBPs.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 CD4+ DO11.10 T-cell proliferation after intranasal antigen exposure. Proliferation of CFSE-labeled CD4+ DO11.10 T cells was assessed by using flow cytometry on day 5. CLNs and PBLNs are lymph nodes draining the upper (nasal mucosa) and lower (lungs) airways, respectively (A and B). The lung was analyzed, being the effector site (lungs), and the popliteal lymph nodes (PLNs) were studied as nondraining lymph nodes (Fig 1, A and B). Pictures are representative of 4 mice per group. The percentage of CFSE-labeled CD4+ DO11.10 T cells is depicted as the percentage of the total CD4 population as a measure of OVA-specific T-cell proliferation (C). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Dendritic cell subset frequency and marker expression in PBLNs after intranasal exposure. The mDC (CD11c-high, GR-1-low) and pDC (CD11c-medium, GR-1-high) populations were gated from the total PBLN cell population (A). The expression of B220 (B) and MHC-II (C) was studied in both populations (Fig 3, A). The total number of mDCs and pDCs and their relative expression of CD80, CD86, and MHC-II are depicted (D). Fig 3, A, B, and C, are representative of 5 animals. Fig 3, D, is representative of 5 animals per group. ∗Significantly different from PBS treatment (P < .05). #Significantly different from OVA treatment (P < .05). APC, Allophycocyanin; FITC, fluorescein isothiocyanate; PerCP, peridinin-chlorophyll-protein. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 3 Dendritic cell subset frequency and marker expression in PBLNs after intranasal exposure. The mDC (CD11c-high, GR-1-low) and pDC (CD11c-medium, GR-1-high) populations were gated from the total PBLN cell population (A). The expression of B220 (B) and MHC-II (C) was studied in both populations (Fig 3, A). The total number of mDCs and pDCs and their relative expression of CD80, CD86, and MHC-II are depicted (D). Fig 3, A, B, and C, are representative of 5 animals. Fig 3, D, is representative of 5 animals per group. ∗Significantly different from PBS treatment (P < .05). #Significantly different from OVA treatment (P < .05). APC, Allophycocyanin; FITC, fluorescein isothiocyanate; PerCP, peridinin-chlorophyll-protein. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 4 Expression of costimulatory molecules by bone marrow–derived dendritic cells in vitro. mDCs were exposed to PBS, CBP (25 μg/mL), or LPS (100 ng/mL). The next day, the expression of CD40, CD80, and CD86 was assessed within the mDC population (CD11c-high, MHC-II positive). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 5 CD80/CD86 is essential for the induction of a TH2 response in PBLN cells after CBP plus OVA exposure. Control mice, mice treated with CTLA-4/Ig, and CD80/CD86-deficient mice were exposed to OVA or CBPs plus OVA. The total numbers of different lymphocyte subtypes and OVA-stimulated production of cytokines was assessed. Data are expressed as means + SEMs (n = 6). ∗Significantly different from the OVA treatment (P < .05). KO, Knockout. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig 6 Dose response of CBPs plus OVA on CD4+ DO11.10 T-cell proliferation. Airway inflammation was determined by neutrophils (A) and TNF-α (B) in bronchoalveolar lavage (BAL) fluid, and proliferation of CFSE-labeled CD4+ DO11.10 T cells was assessed in PBLNs at day 5 (C and D). Data are expressed as means + SEMs (n = 5). ∗Significantly different ∗from OVA (p < .01), #from CBP (20) plus OVA (P < .01), and $from all the other CBP plus OVA concentrations (P < .05). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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