Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response
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{"title"=>"Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response", "type"=>"journal", "authors"=>[{"first_name"=>"Tracy J.", "last_name"=>"Ruckwardt", "scopus_author_id"=>"7801656918"}, {"first_name"=>"Allison M.W.", "last_name"=>"Malloy", "scopus_author_id"=>"36637921100"}, {"first_name"=>"Kaitlyn M.", "last_name"=>"Morabito", "scopus_author_id"=>"56060408700"}, {"first_name"=>"Barney S.", "last_name"=>"Graham", "scopus_author_id"=>"7201610365"}], "year"=>2014, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "scopus"=>"2-s2.0-84895766412", "sgr"=>"84895766412", "pui"=>"372548645", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "pmid"=>"24550729", "doi"=>"10.1371/journal.ppat.1003934"}, "id"=>"530efdad-fdff-3097-8f3d-238f83b683b9", "abstract"=>"CD103+ and CD11b+ populations of CD11c+MHCIIhi murine dendritic cells (DCs) have been shown to carry antigens from the lung through the afferent lymphatics to mediastinal lymph nodes (MLN). We compared the responses of these two DC populations in neonatal and adult mice following intranasal infection with respiratory syncytial virus. The response in neonates was dominated by functionally-limited CD103+ DCs, while CD11b+ DCs were diminished in both number and function compared to adults. Infecting mice at intervals through the first three weeks of life revealed an evolution in DC phenotype and function during early life. Using TCR transgenic T cells with two different specificities to measure the ability of CD103+ DC to induce epitope-specific CD8+ T cell responses, we found that neonatal CD103+ DCs stimulate proliferation in a pattern distinct from adult CD103+ DCs. Blocking CD28-mediated costimulatory signals during adult infection demonstrated that signals from this costimulatory pathway influence the hierarchy of the CD8+ T cell response to RSV, suggesting that limited costimulation provided by neonatal CD103+ DCs is one mechanism whereby neonates generate a distinct CD8+ T cell response from that of adults.", "link"=>"http://www.mendeley.com/research/quantitative-qualitative-deficits-neonatal-lungmigratory-dendritic-cells-impact-generation-cd8-t-cel", "reader_count"=>52, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>18, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>18, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>27, "Medicine and Dentistry"=>7, "Immunology and Microbiology"=>13}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>13}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1385792"], "description"=>"<p>Soluble ovalbumin-FITC protein (A and B) or ovalbumin-DQ (C and D) were co-administered at the time of RSV infection and the percent of the CD103+ and CD11b+ DC populations positive for FITC expression (A or B) or shown to be processing antigen by unquenching of ova-DQ were measured in the MLN at days 1, 2, and 3 post-infection. Data are combined from two independent experiments using pooled lymph node samples (3–7 mice/pool depending on age and availability) and error bars indicate the SEM. * p≤0.05, **p≤0.01, ***p≤0.001, **** p≤0.0001 by two-way ANOVA and Tukey's multiple comparisons test.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "Antigen-presenting cells", "t cells", "Immune system", "Lymphoid organs", "immunity", "Adaptive immunity", "Immunity to infections", "Innate immunity", "Antigen processing and recognition", "Immune response", "immunopathology", "Major histocompatibility complex", "microbiology", "Virology", "Animal models of infection", "Host-pathogen interaction", "Model organisms", "Animal models", "mouse", "soluble", "antigen"], "article_id"=>934541, "categories"=>["Biological Sciences"], "users"=>["Tracy J. Ruckwardt", "Allison M. W. Malloy", "Kaitlyn M. Morabito", "Barney S. Graham"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003934.g003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Uptake_and_processing_of_soluble_antigen_is_age_dependent_/934541", "title"=>"Uptake and processing of soluble antigen is age-dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 02:59:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1385787"], "description"=>"<p>CD103+ and CD11b+ DC populations in the MLN three days post-RSV infection were measured in mice of different ages. A) DC populations as a percent of CD11c+-gated cells of mice infected at the indicated age. B) Ratio of CD103+ to CD11b+ cells in the MHC Class II high gate. C) Total number of DC cells acquired on the flow cytometer per mouse after running samples to completion. Data in A and C are representative of three experiments using mice at available ages, and B represents data compiled from three independent experiments. Groups were compared using a two-way or one-way ANOVA and Tukey's multiple comparisons tests in GraphPad Prism and significant differences within the 7–21 day transition period are indicated (* p≤0.05, ** p≤0.01, ***p≤0.001, **** p≤0.0001). Error bars represent the SEM.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "Antigen-presenting cells", "t cells", "Immune system", "Lymphoid organs", "immunity", "Adaptive immunity", "Immunity to infections", "Innate immunity", "Antigen processing and recognition", "Immune response", "immunopathology", "Major histocompatibility complex", "microbiology", "Virology", "Animal models of infection", "Host-pathogen interaction", "Model organisms", "Animal models", "mouse", "dendritic", "responses"], "article_id"=>934537, "categories"=>["Biological Sciences"], "users"=>["Tracy J. Ruckwardt", "Allison M. W. Malloy", "Kaitlyn M. Morabito", "Barney S. Graham"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003934.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lung_migratory_dendritic_cell_responses_change_dramatically_during_early_life_/934537", "title"=>"Lung-migratory dendritic cell responses change dramatically during early life.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 02:59:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1385786"], "description"=>"<p>Percent of infected (GFP+) dendritic cell populations in the lung (A and B) and the posterior mediastinal lymph node (MLN, C and D) at days 1–3 post-infection. Lung and MLN DC populations were gated as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003934#ppat.1003934.s001\" target=\"_blank\">Figure S1</a> and <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003934#ppat.1003934.s002\" target=\"_blank\">S2</a>, respectively. Percent GFP+ of CD103+ DCs (A and C) and CD11b+ DCs (B and D) was determined by comparison to mice infected at the same time with wtRSV. Data is representative of two experiments done with two pooled samples of 3–7 mice each and the error bars represent the SEM. * p≤0.05, **p≤0.01, ***p≤0.001, ns is no significance by two-way ANOVA and Sidak's multiple comparisons test.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "Antigen-presenting cells", "t cells", "Immune system", "Lymphoid organs", "immunity", "Adaptive immunity", "Immunity to infections", "Innate immunity", "Antigen processing and recognition", "Immune response", "immunopathology", "Major histocompatibility complex", "microbiology", "Virology", "Animal models of infection", "Host-pathogen interaction", "Model organisms", "Animal models", "mouse", "migratory", "dendritic", "populations", "draining", "mediastinal", "lymph"], "article_id"=>934535, "categories"=>["Biological Sciences"], "users"=>["Tracy J. Ruckwardt", "Allison M. W. Malloy", "Kaitlyn M. Morabito", "Barney S. Graham"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003934.g001", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RSV_infection_of_lung_migratory_dendritic_cell_populations_in_the_lung_and_draining_mediastinal_lymph_node_/934535", "title"=>"RSV infection of lung migratory dendritic cell populations in the lung and draining mediastinal lymph node.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 02:59:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1385794"], "description"=>"<p>A) Evaluation of the Class II high populations of neonatal (7 days old) vs. adult mice shows differences in composition and phenotype of DC populations. B) Costimulatory molecule (CD86, CD80 and CD70) expression was measured by flow cytometry on CD103+ and CD11b+ DCs three days post-infection at the indicated age and the mean fluorescence intensity (MFI) is displayed. Data are representative of three experiments using two to three samples of lymph nodes pooled from 3–7 mice. Error bars indicate the SEM, and all data was analyzed using one-way ANOVA with Tukey's multiple comparisons test (* p≤0.05, ** p≤0.01, *** p≤0.001, **** p≤0.0001).</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "Antigen-presenting cells", "t cells", "Immune system", "Lymphoid organs", "immunity", "Adaptive immunity", "Immunity to infections", "Innate immunity", "Antigen processing and recognition", "Immune response", "immunopathology", "Major histocompatibility complex", "microbiology", "Virology", "Animal models of infection", "Host-pathogen interaction", "Model organisms", "Animal models", "mouse", "phenotypic", "dc", "populations", "mln", "days"], "article_id"=>934543, "categories"=>["Biological Sciences"], "users"=>["Tracy J. Ruckwardt", "Allison M. W. Malloy", "Kaitlyn M. Morabito", "Barney S. Graham"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003934.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Age_dependent_phenotypic_changes_in_the_CD103_and_CD11b_DC_populations_in_the_MLN_three_days_post_infection_/934543", "title"=>"Age-dependent phenotypic changes in the CD103+ and CD11b+ DC populations in the MLN three days post-infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 02:59:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1385795"], "description"=>"<p>A) CFSE-labeled TCR transgenic CD8+ T cells specific for K<sup>d</sup>M2<sub>82–90</sub> or D<sup>b</sup>M<sub>187–195</sub> were co-cultured in a 10∶1 ratio with CD103+ dendritic cells sorted from the lymph nodes of RSV infected adults or neonates one day after infection. The percent of cells that proliferated following three days in co-culture was calculated using the proliferation module in FlowJo 9.4.10. Negative control samples consisted of TCR Tg T cells co-cultured with splenocytes with no exogenous peptide, and positive control samples were co-cultured with splenocytes and 10<sup>−6</sup>M of specific peptide. B) Comparison of the ratio of proliferation (percent of K<sup>d</sup>M2<sub>82–90</sub>-specific cells that proliferated/percent of D<sup>b</sup>M<sub>187–195</sub>-specific cells that proliferated) induced by flow-sorted neonatal vs. adult CD103+DCs. Groups were compared using a student's t-test.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "Antigen-presenting cells", "t cells", "Immune system", "Lymphoid organs", "immunity", "Adaptive immunity", "Immunity to infections", "Innate immunity", "Antigen processing and recognition", "Immune response", "immunopathology", "Major histocompatibility complex", "microbiology", "Virology", "Animal models of infection", "Host-pathogen interaction", "Model organisms", "Animal models", "mouse", "dcs", "differentially", "induce", "rsv-specific", "adaptive"], "article_id"=>934544, "categories"=>["Biological Sciences"], "users"=>["Tracy J. Ruckwardt", "Allison M. W. Malloy", "Kaitlyn M. Morabito", "Barney S. Graham"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003934.g005", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neonatal_CD103_DCs_differentially_induce_RSV_specific_adaptive_CD8_T_cell_responses_/934544", "title"=>"Neonatal CD103+ DCs differentially induce RSV-specific adaptive CD8+ T cell responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 02:59:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1385807", "https://ndownloader.figshare.com/files/1385808", "https://ndownloader.figshare.com/files/1385809", "https://ndownloader.figshare.com/files/1385810", "https://ndownloader.figshare.com/files/1385811", "https://ndownloader.figshare.com/files/1385812", "https://ndownloader.figshare.com/files/1385813", "https://ndownloader.figshare.com/files/1385814"], "description"=>"<div><p>CD103+ and CD11b+ populations of CD11c+MHCIIhi murine dendritic cells (DCs) have been shown to carry antigens from the lung through the afferent lymphatics to mediastinal lymph nodes (MLN). We compared the responses of these two DC populations in neonatal and adult mice following intranasal infection with respiratory syncytial virus. The response in neonates was dominated by functionally-limited CD103+ DCs, while CD11b+ DCs were diminished in both number and function compared to adults. Infecting mice at intervals through the first three weeks of life revealed an evolution in DC phenotype and function during early life. Using TCR transgenic T cells with two different specificities to measure the ability of CD103+ DC to induce epitope-specific CD8+ T cell responses, we found that neonatal CD103+ DCs stimulate proliferation in a pattern distinct from adult CD103+ DCs. Blocking CD28-mediated costimulatory signals during adult infection demonstrated that signals from this costimulatory pathway influence the hierarchy of the CD8+ T cell response to RSV, suggesting that limited costimulation provided by neonatal CD103+ DCs is one mechanism whereby neonates generate a distinct CD8+ T cell response from that of adults.</p></div>", "links"=>[], "tags"=>["immunology", "Immune cells", "Antigen-presenting cells", "t cells", "Immune system", "Lymphoid organs", "immunity", "Adaptive immunity", "Immunity to infections", "Innate immunity", "Antigen processing and recognition", "Immune response", "immunopathology", "Major histocompatibility complex", "microbiology", "Virology", "Animal models of infection", "Host-pathogen interaction", "Model organisms", "Animal models", "mouse", "qualitative", "deficits", "neonatal", "lung-migratory", "dendritic", "cells"], "article_id"=>934552, "categories"=>["Biological Sciences"], "users"=>["Tracy J. Ruckwardt", "Allison M. W. Malloy", "Kaitlyn M. Morabito", "Barney S. Graham"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003934.s001", "https://dx.doi.org/10.1371/journal.ppat.1003934.s002", "https://dx.doi.org/10.1371/journal.ppat.1003934.s003", "https://dx.doi.org/10.1371/journal.ppat.1003934.s004", "https://dx.doi.org/10.1371/journal.ppat.1003934.s005", "https://dx.doi.org/10.1371/journal.ppat.1003934.s006", "https://dx.doi.org/10.1371/journal.ppat.1003934.s007", "https://dx.doi.org/10.1371/journal.ppat.1003934.s008"], "stats"=>{"downloads"=>13, "page_views"=>31, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitative_and_Qualitative_Deficits_in_Neonatal_Lung_Migratory_Dendritic_Cells_Impact_the_Generation_of_the_CD8_T_Cell_Response_/934552", "title"=>"Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-13 02:59:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1385801"], "description"=>"<p>A) Mice were infected with RSV on day 0 and subsequently given IP injections of 20 µg each of antibodies against CD80 and CD86 at the indicated day post-infection. Epitope-specific CD8+ T cell responses were measured by surface and tetramer staining at 7 days post-infection. All groups were compared using a two-way ANOVA and Tukey's multiple comparisons tests, and there were no significant differences in the D<sup>b</sup>M<sub>187–195</sub> response. Differences between the K<sup>d</sup>M2<sub>82–90</sub> response on Day 2 and other groups are indicated below the figure (* p≤0.05, *** p≤0.001, **** p≤0.0001). B) The response ratio/immunodominance profile of CD8+ T cell responses was obtained for each mouse by dividing the K<sup>d</sup>M2<sub>82–90</sub> response by the response to D<sup>b</sup>M<sub>187–195</sub>. * indicates p≤0.05 following one-way ANOVA and Dunnett's multiple comparisons test. C) Day 7 CD8+ T cell responses of mice injected with the indicated dose of anti-CD80 and CD86 at day 2 post-infection or isotype control antibodies (either 50 µg or 20 µg). All groups were compared using a two-way ANOVA and Tukey's multiple comparisons tests. Differences in the K<sup>d</sup>M2<sub>82–90</sub> response between the 50 and 25 µg groups and all other groups are indicated below the figure (ns not significant, ** p≤0.01, and **** p≤0.0001). The D<sup>b</sup>M<sub>187–195</sub> responses are significantly different between both the 50 and the 25 µg groups and isotype (p≤0.01) only. D) CD8+ T cell response ratios of mice treated with each dose of anti-CD80 and CD86 antibodies. Groups were compared with a one-way ANOVA and Tukey's multiple comparisons test (** p≤0.01, *** p≤0.001, **** p≤0.0001), and all error bars represent the SEM.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "Antigen-presenting cells", "t cells", "Immune system", "Lymphoid organs", "immunity", "Adaptive immunity", "Immunity to infections", "Innate immunity", "Antigen processing and recognition", "Immune response", "immunopathology", "Major histocompatibility complex", "microbiology", "Virology", "Animal models of infection", "Host-pathogen interaction", "Model organisms", "Animal models", "mouse", "cd28-mediated", "costimulatory", "signals", "differentially"], "article_id"=>934546, "categories"=>["Biological Sciences"], "users"=>["Tracy J. Ruckwardt", "Allison M. W. Malloy", "Kaitlyn M. Morabito", "Barney S. Graham"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003934.g006", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Modulating_CD28_mediated_costimulatory_signals_differentially_affects_K_d_M2_82_8211_90_and_D_b_M_187_8211_195_specific_responses_/934546", "title"=>"Modulating CD28-mediated costimulatory signals differentially affects K<sup>d</sup>M2<sub>82–90</sub> and D<sup>b</sup>M<sub>187–195</sub>-specific responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 02:59:31"}

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Relative Metric

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