OX40 Facilitates Control of a Persistent Virus Infection
Publication Date
September 06, 2012
Journal
PLOS Pathogens
Authors
Tobias Boettler, Friedrich Moeckel, Yang Cheng, Maximilian Heeg, et al
Volume
8
Issue
9
Pages
e1002913
DOI
http://doi.org/10.1371/journal.ppat.1002913
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1002913
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22969431
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435255
Europe PMC
http://europepmc.org/abstract/MED/22969431
Web of Science
000309816500020
Scopus
84866929046
Mendeley
http://www.mendeley.com/research/ox40-facilitates-control-persistent-virus-infection
Events
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Mendeley | Further Information

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CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["http://files.figshare.com/582132/Figure_7.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "users"=>["Friedrich Moeckel", "Maximilian Heeg", "Shahram Salek-Ardakani", "Michael Croft", "Shane Crotty", "Yang Cheng", "Matthias G. von Herrath", "Tobias Boettler"], "links"=>[], "tags"=>["regulates", "bcl-2"], "title"=>"<p>OX40 regulates T cell survival and Bcl-2 and Bcl-xL.</p>", "figshare_url"=>"http://figshare.com/articles/_OX40_regulates_T_cell_survival_and_Bcl_2_and_Bcl_xL_/252624", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.ppat.1002913.g007"], "published_date"=>"2013-02-19 23:57:12", "article_id"=>252624, "categories"=>["Immunology", "Infectious Diseases"], "description"=>"<p >(A&#8211;D) Fas, Annexin V and active caspase 3 analyses were performed to detect apoptotic signals in co-transferred TCRtg cells (WT red, OX40&#8722;/&#8722; black) and endogenous CD4 and CD8 T cells (grey area) after LCMV cl13 infection. (A, B) Representative Annexin V stainings and bar graphs showing Annexin V MFI on CD4 smtg cells on day 8 p.i. (A) and on CD8 P14 cells on day 10 p.i. (B). (C) Representative Fas staining on day 8 p.i. and bar graph showing Fas expression 5, 8, and 20 days post infection on CD4 smtg cells. (D) Representative intracellular staining for active caspase 3 and bar graph showing Caspase 3 MFI on day 8 p.i. on CD4 smtg cells. Data are derived from 3 independent CD4 smtg cell transfer experiments and one CD8 P14 transfer experiment. (E) Analysis of expression of anti-apoptotic molecules Bcl-2 and Bcl-xL on virus-specific CD4 T cells of WT and OX40&#8722;/&#8722; mice (WT red, OX40&#8722;/&#8722; black) via intracellular protein staining 8 and 20 days post persistent LCMV infection. Data are derived from 1&#8211;2 independent experiments per time point.</p>"}
  • {"files"=>["http://files.figshare.com/581771/Figure_3.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "users"=>["Friedrich Moeckel", "Maximilian Heeg", "Shahram Salek-Ardakani", "Michael Croft", "Shane Crotty", "Yang Cheng", "Matthias G. von Herrath", "Tobias Boettler"], "links"=>[], "tags"=>["Infectious diseases", "immunology"], "title"=>"<p>Lack of virus control in OX40&#8722;/&#8722; mice.</p>", "figshare_url"=>"http://figshare.com/articles/_Lack_of_virus_control_in_OX40_8722_8722_mice_/252259", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.ppat.1002913.g003"], "published_date"=>"2013-02-19 23:49:30", "article_id"=>252259, "categories"=>["Immunology", "Infectious Diseases"], "description"=>"<p >(A) Serum, (B) kidney, (C) lung and (D) liver samples were harvested on days 10, 20, 50, 80 and 120 post infection and viral loads were determined by plaque assay. Statistical analysis for viral titers was performed using log rank test, undetectable viral titers were defined as endpoint. Data are derived from a total of 8 independent experiments, 1&#8211;2 experiments per time point.</p>"}
  • {"files"=>["http://files.figshare.com/581683/Figure_2.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "users"=>["Friedrich Moeckel", "Maximilian Heeg", "Shahram Salek-Ardakani", "Michael Croft", "Shane Crotty", "Yang Cheng", "Matthias G. von Herrath", "Tobias Boettler"], "links"=>[], "tags"=>["humoral"], "title"=>"<p>Impaired humoral immune response in OX40&#8722;/&#8722; mice.</p>", "figshare_url"=>"http://figshare.com/articles/_Impaired_humoral_immune_response_in_OX40_8722_8722_mice_/252176", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.ppat.1002913.g002"], "published_date"=>"2013-02-19 23:48:22", "article_id"=>252176, "categories"=>["Immunology", "Infectious Diseases"], "description"=>"<p >(A&#8211;H) Follicular T helper cell (Tfh) and germinal center responses were analyzed 8 respectively 20 days post LCMV cl13 infection in WT (black bars and lines) and OX40&#8722;/&#8722; mice (white bars and dashed lines) and compared to na&#239;ve WT mice (grey bars). (A) Number of Bcl6+CXCR5+ Tfh cells per spleen, (B) representative FACS-plots gated on CD4 T cells. (C) Number of LCMV-specific follicular helper CD4 T cells per spleen, (D) representative FACS-plots gated on CD4 T cells. (E) Number of germinal center B cells per spleen, (F) representative FACS-plots gated on B cells showing germinal center B cell populations. (G) Number of plasma cells per spleen, (H) representative FACS-plots gated on B cells showing plasma cell populations. Representative results from 1 of 2&#8211;3 independent experiments are illustrated. (I) LCMV-specific IgG antibody titers were analyzed by Elisa on days 10, 20, 50, 80 and 120 post infection (n&#8202;=&#8202;4&#8211;10 per group and time point). Data are derived from a total of 7 independent experiments, 1&#8211;2 experiments per time point.</p>"}
  • {"files"=>["http://files.figshare.com/581915/Figure_5.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "users"=>["Friedrich Moeckel", "Maximilian Heeg", "Shahram Salek-Ardakani", "Michael Croft", "Shane Crotty", "Yang Cheng", "Matthias G. von Herrath", "Tobias Boettler"], "links"=>[], "tags"=>["accumulation"], "title"=>"<p>OX40 promotes T cell accumulation in a dose dependent manner.</p>", "figshare_url"=>"http://figshare.com/articles/_OX40_promotes_T_cell_accumulation_in_a_dose_dependent_manner_/252409", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.ppat.1002913.g005"], "published_date"=>"2013-02-19 23:51:51", "article_id"=>252409, "categories"=>["Immunology", "Infectious Diseases"], "description"=>"<p >(A, B) Equal numbers of WT (CD45.1+CD45.2&#8722;) and OX40&#8722;/&#8722; (CD45.1+CD45.2+) smtg were transferred into the same WT recipients (CD45.1&#8722;CD45.2+) prior to LCMV cl13 infection. Splenocytes were harvested on days 5, 8, 10 and 20 post infection (n&#8202;=&#8202;4&#8211;8 for each time point) and (A) frequencies of OX40&#8722;/&#8722; smtg and WT smtg were determined within the CD4 gate by flow cytometry. (B) Frequencies shown in FACS-plots are percent of CD45.1+ (transferred cells); plots are gated on CD4 T cells. (C&#8211;E) OX40+/+ (WT, black bars), OX40+/&#8722; (Het, grey bars) and OX40&#8722;/&#8722; (KO, white bars) smtg were separately transferred into WT recipients prior to LCMV cl13 infection and (C) frequencies of WT, Het and KO smtg cells within the CD4 gate were determined 10 days post infection (n&#8202;=&#8202;5 per group). (D) OX40 expression on WT, Het and KO smtg cells was determined 10 days post infection by flow cytometry (n&#8202;=&#8202;5 per group). (E) Representative FACS-plots showing transferred cells and OX40 expression gated on CD4 T cells. (F) Equal numbers of CD45.1/2 mismatched WT and OX40&#8722;/&#8722; P14 cells were co-transferred into WT recipients prior to LCMV cl13 infection and frequencies of OX40&#8722;/&#8722; P14 and WT P14 were determined within the transferred P14 population by flow cytometry on day 3, 5, 8 and 20 post infection (n&#8202;=&#8202;4&#8211;5 for each time point). (G, H) Similar co-transfer experiments with CD4 and CD8 T cell were performed in order to compare the role of OX40 on a single cell level in acute and chronic LCMV infection. Graph shows percentage of transferred OX40&#8722;/&#8722; CD4 respectively OX40&#8722;/&#8722; CD8 T cells of all transferred T-Cells 8 days post infection. Data are derived from 2&#8211;3 independent CD4 smtg cell transfer experiments per time point and 1&#8211;3 independent CD8 P14 cell transfer experiments per time point.</p>"}
  • {"files"=>["http://files.figshare.com/581580/Figure_1.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "users"=>["Friedrich Moeckel", "Maximilian Heeg", "Shahram Salek-Ardakani", "Michael Croft", "Shane Crotty", "Yang Cheng", "Matthias G. von Herrath", "Tobias Boettler"], "links"=>[], "tags"=>["anti-viral", "cd4", "cd8", "responses"], "title"=>"<p>Impaired anti-viral CD4 and CD8 T cell responses in OX40&#8722;/&#8722; mice.</p>", "figshare_url"=>"http://figshare.com/articles/_Impaired_anti_viral_CD4_and_CD8_T_cell_responses_in_OX40_8722_8722_mice_/252059", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.ppat.1002913.g001"], "published_date"=>"2013-02-19 23:47:06", "article_id"=>252059, "categories"=>["Immunology", "Infectious Diseases"], "description"=>"<p>WT (black circles) and OX40−/− (white circles) mice were intravenously infected with 2×10<sup>6</sup> PFU of LCMV cl13. (A) Loss of body weight was measured twice weekly as a marker for disease severity. (B, C) Virus-specific splenic T cell populations in WT and OX40&#8722;/&#8722; mice were analyzed 20 days post infection using GP33-pentamers (B, CD8) and GP66-tetramers (C, CD4). (D&#8211;H) Splenocytes of infected mice were harvested 10, 20 and 50 days post infection. Intracellular cytokine stainings (ICCS) were performed following in vitro stimulation with immunodominant CD8 (D&#8211;F) and CD4 (G, H) epitopes as illustrated. (I) Representative ICCS staining following GP61 stimulation, gated on CD4 T cells. Data are derived from a total of 7 independent experiments, 1&#8211;2 experiments per time point.</p>"}
  • {"files"=>["http://files.figshare.com/582008/Figure_6.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "users"=>["Friedrich Moeckel", "Maximilian Heeg", "Shahram Salek-Ardakani", "Michael Croft", "Shane Crotty", "Yang Cheng", "Matthias G. von Herrath", "Tobias Boettler"], "links"=>[], "tags"=>["antiviral", "dispensable", "proliferation"], "title"=>"<p>OX40 is dispensable for T cell proliferation and direct antiviral T cell function.</p>", "figshare_url"=>"http://figshare.com/articles/_OX40_is_dispensable_for_T_cell_proliferation_and_direct_antiviral_T_cell_function_/252508", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.ppat.1002913.g006"], "published_date"=>"2013-02-19 23:54:37", "article_id"=>252508, "categories"=>["Immunology", "Infectious Diseases"], "description"=>"<p >(A) WT and OX40&#8722;/&#8722; P14 cells were labeled with CFSE prior to injection in WT recipients. Graph is showing CFSE dilution of congenically marked TCR transgenic (WT red, OX40&#8722;/&#8722; black) and unlabeled endogenous CD8 T cells (grey area) 5 days post infection. (B, C) CD45.1/2 mismatched WT and OX40&#8722;/&#8722; TCRtg cells were co-transferred into WT recipients prior to LCMV cl13 infection and BrdU was injected intraperitoneally on day 6 post infection according to the manufacturer's instructions. Cells were harvested and BrdU staining was detected by flow cytometry to visualize cells that had proliferated. Data are representative for 1 out of 2 independent experiments. (D) Intracellular cytokine staining (ICCS) for IFN-&#947;, IL-21 and IL-2 was performed 10 days post infection following peptide stimulation (n&#8202;=&#8202;5 per group). (E) Representative FACS-plots showing IFN-&#947; and IL-21 production of WT, Het and KO smtg cells. (F) Intracellular cytokine staining (ICCS) for IFN-&#947; following GP33 peptide stimulation on congenically marked TCR transgenic CD8 T cells (P14) transferred into WT recipients was performed 5 and 8 days post infection (n&#8202;=&#8202;4&#8211;5 per group). Data are derived from 2 independent CD4 smtg cell transfer experiments and 2 independent CD8 P14 cell transfer experiments.</p>"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[322, 550, 671, 773, 864, 955, 1048, 1135, 1223, 1308, 1387, 1465, 1534, 1602, 1673, 1744, 1813, 1885, 1955, 2026, 2093, 2160, 2228, 2290, 2349]}, {"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[312, 555, 680, 785, 880, 965, 1057, 1142, 1230, 1312, 1394, 1471, 1547, 1613, 1681, 1743, 1805, 1871, 1941, 2010, 2071, 2128, 2202, 2266, 2323]}, {"subject_area"=>"/Biology and life sciences/Microbiology", "average_usage"=>[339, 580, 709, 814, 907, 1003, 1095, 1190, 1286, 1375, 1466, 1546, 1622, 1694, 1765, 1830, 1902, 1978, 2054, 2122, 2194, 2269, 2330, 2388, 2460]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[312, 547, 668, 769, 861, 953, 1046, 1135, 1224, 1307, 1388, 1464, 1536, 1606, 1676, 1744, 1812, 1882, 1954, 2020, 2089, 2155, 2218, 2282, 2344]}, {"subject_area"=>"/Medicine and health sciences/Immunology", "average_usage"=>[307, 545, 668, 765, 855, 943, 1029, 1113, 1202, 1285, 1361, 1439, 1506, 1571, 1636, 1706, 1772, 1837, 1901, 1969, 2031, 2096, 2160, 2228, 2287]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[314, 554, 687, 796, 891, 983, 1075, 1170, 1261, 1340, 1422, 1504, 1574, 1647, 1715, 1786, 1848, 1919, 1990, 2053, 2115, 2197, 2258, 2333, 2395]}]}
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