Regulation of CD4+ and CD8+ Effector Responses by Sprouty-1
Publication Date
November 15, 2012
Journal
PLOS ONE
Authors
Sam Collins, Adam Waickman, Albert Basson, Abraham Kupfer, et al
Volume
7
Issue
11
Pages
e49801
DOI
http://doi.org/10.1371/journal.pone.0049801
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0049801
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23166773
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499516
Europe PMC
http://europepmc.org/abstract/MED/23166773
Web of Science
000311272300070
Scopus
84869223705
Mendeley
http://www.mendeley.com/research/regulation-cd4-cd8-effector-responses-sprouty1
Events
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/542494"], "description"=>"<p>Western blot analysis of Spry1 and actin in previously activated 5C.C7 T cells stimulated with anti-CD3 with or without CSA treatment. <b>B.</b> Real-Time PCR analysis of Spry1 expression in wild type, Egr-3<sup>−/−</sup> and Egr-3 overexpressing CD4<sup>+</sup> T cells stimulated with anti-CD3 and anti-CD28. (N = 3). Mock treated cells were stimulated with anti-CD28 alone. <b>C.</b> CHiP analysis of Egr-3 binding to the Sprouty-1 promoter following PMA and Ionomycin stimulation. Error bars represent one standard deviation of the mean. All experiments were performed at least three times.</p>", "links"=>[], "tags"=>["spry1", "regulated"], "article_id"=>212987, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049801.g001", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TCR_induced_Spry1_is_regulated_by_Egr_3_A_/212987", "title"=>"TCR-induced Spry1 is regulated by Egr-3. A.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:49:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/542796"], "description"=>"<p>Spry1 null and wild type spleens were expanded <i>in vitro</i> with anti-CD3, spleens were rechallenged with anti-CD3. <b>A.</b> CFSE dilution of wild type and Spry1 null CD8<sup>+</sup> T cells. Intracellular cytokine secretion assay was performed for IFNγ (<b>B</b>) and Granzyme-B (<b>C</b>). A mixture of CFSE high labeled, peptide pulsed splenocytes and CFSE low unlabeled splenocytes were injected I. V. into either wild type or Spry1<sup>Flox/Flox</sup> Lck Cre mice. Sixteen hours later splenocytes were analyzed by flow cytometry for the presence of CFSE high and CFSE low cells. <b>D.</b> Representative histogram data (for individual mice) from unvaccinated and vaccinated Wt and Spry1<sup>Flox/Flox</sup> Lck Cre mice. Percentages are representative of CFSE high and CFSE low populations. <b>E.</b> Graphical representation of data from five wild type and five Spry1<sup>Flox/Flox</sup> Lck Cre mice. Error bars represent one standard deviation of the mean. P values indicate statistical significance by student t-test. All experiments were performed at least three times.</p>", "links"=>[], "tags"=>["null", "cells", "enhanced", "effector"], "article_id"=>213289, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049801.g004", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spry1_null_CD8_T_cells_have_enhanced_effector_function_/213289", "title"=>"Spry1 null CD8<sup>+</sup> T cells have enhanced effector function.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:54:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/543020"], "description"=>"<p>Jurkat T cells were transfected with either control vector (Lenti-CTRL), Sprouty-1 overexpression vector (Lenti-Spry1) or a mutant Spry1 overexpression vector that lacks the c terminal domain (Lenti-DC104 Spry1). Jurkats were also tranfected with either an IL-2 driving luciferase construct (<b>A</b>), an AP-1 driving luciferase construct (<b>B</b>), an NF-AT driving luciferase construct(<b>C</b>), or an NF-κB driving luciferase construct (<b>D</b>). Jurkats were stimulated with anti-CD3 and luciferase activity was measured. Data are presented as fold increase in luciferase over unstimulated. Error bars represent one standard deviation of the mean. P values indicate statistical significance by student t-test. All experiments were performed at least three times.</p>", "links"=>[], "tags"=>["overexpression", "suppresses", "nf-at"], "article_id"=>213510, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049801.g006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spry1_overexpression_suppresses_IL_2_AP_1_and_NF_AT_signaling_/213510", "title"=>"Spry1 overexpression suppresses IL-2, AP-1, and NF-AT signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:58:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/542904"], "description"=>"<p><b>A.</b> Western blot analysis of PLC-γ and LAT phosphorylation in wild type and Spry1<sup>flox/flox</sup> Lck cre CD4<sup>+</sup> T cells following ten-minute stimulation with anti-CD3 and anti-CD28. <b>B.</b> Graphical representation of Phospho-PLCγ and Phospho-LAT levels as measured by densitometry presented as ratio of signal to Actin levels. <b>C</b>. IP3 levels in wild type and Spry1 null CD4<sup>+</sup> T cells following five-minute stimulation with anti-CD3. <b>D.</b> Western blot analysis of ERK phosphorylation in wild type and Spry1<sup>flox/flox</sup> Lck cre CD4<sup>+</sup> T cells following 5 minute stimulation with anti-CD3. <b>E.</b> Western blot analysis of ERK phosphorylation in control vector or Spry1 overexpression vector transduced jurkat T cells following 2 and 5 minute stimulation with anti-CD3. Error bars represent one standard deviation of the mean. P values indicate statistical significance by student t-test. All experiments were performed at least three times. Data are representative of 3 mice per group.</p>", "links"=>[], "tags"=>["null", "cells", "enhanced", "tcr"], "article_id"=>213396, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049801.g005", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spry1_null_CD4_T_cells_have_enhanced_TCR_signaling_/213396", "title"=>"Spry1 null CD4<sup>+</sup> T cells have enhanced TCR signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:56:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/543228"], "description"=>"<p>Wild type and Spry1 null mice were subcutaneously injected with EL-4 tumor cells. Mice were monitored for (<b>A</b>) tumor free survival and (<b>B</b>) tumor volume. All experiments were performed at least three times. (<b>C</b>) Wt and Spry1 null T cell mice were injected IV with 250,000 B16 melanoma cells, 14 days later mice were sacrificed and lung tumors were counted. P values indicate statistical significance by student t-test. All experiments were performed at least three times. Data are representative of 10 mice per group.</p>", "links"=>[], "tags"=>["null", "mice", "enhanced", "clearance", "el-4"], "article_id"=>213712, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049801.g008", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spry1_null_mice_have_enhanced_clearance_of_EL_4_tumor_cells_/213712", "title"=>"Spry1 null mice have enhanced clearance of EL-4 tumor cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 01:01:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/543124"], "description"=>"<p>Wild type and Spry1 null mice were subcutaneously injected with a 1∶1 mixture of irradiated EL-4 tumor cells expressing ovalbumin and B16 cells expressing GM-CSF. Seven days later inguinal lymph nodes were isolated and stained with CD8 and ovalbumin specific tetramer. (<b>A</b>) Flow cytometric data from lymph nodes of one wild type and one Spry1 null mouse. Gates are set on CD8<sup>+</sup> and CD44<sup>+</sup> cells. (<b>B</b>) Graphical representation of data from four wild type and four Spry1 null mice. P values indicate statistical significance by student t-test. All experiments were performed at least three times.</p>", "links"=>[], "tags"=>["null", "mice", "percentages", "ova", "cells"], "article_id"=>213611, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049801.g007", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spry1_null_mice_have_increased_percentages_of_OVA_specific_CD8_T_cells_following_vaccination_/213611", "title"=>"Spry1 null mice have increased percentages of OVA specific CD8<sup>+</sup> T cells following vaccination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 01:00:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/542691"], "description"=>"<p>Spry1 null and wild type spleens were expanded <i>in vitro</i> with anti-CD3; CD4<sup>+</sup> T cells were isolated and rechallenged with increasing doses of anti-CD3. <b>A.</b> IL-2 production by CD4<sup>+</sup> T cells was determined by ELISA. <b>B.</b> CFSE dilution of CD4<sup>+</sup> wild type and Spry1 null CD4<sup>+</sup> T cells. <b>C.</b> IFNγ production was determined by intracellular cytokine secretion assay. % of Max indicates the fraction of the total cells at a given fluorescent intensity. <b>D.</b> Following expansion Spry1 null and wild type spleens were stimulated with increasing doses of ionomycin, briefly rested and rechallenged with anti-CD3. Resistance to ionomycin-induced anergy is displayed as percentage of IL-2 produced following ionomycin treatment and rechallenge compared to rechallenged alone. Error bars represent one standard deviation of the mean. P values indicate statistical significance by student t-test. All experiments were performed at least three times. Data are representative of 3 mice per group.</p>", "links"=>[], "tags"=>["null", "cells", "enhanced", "effector"], "article_id"=>213180, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049801.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spry1_null_CD4_T_cells_have_enhanced_effector_function_/213180", "title"=>"Spry1 null CD4<sup>+</sup> T cells have enhanced effector function.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:53:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/290335", "https://ndownloader.figshare.com/files/290405", "https://ndownloader.figshare.com/files/290445"], "description"=>"<div><p>TCR-induced NF-AT activation leads to the expression of both activating and inhibitory proteins. Previously, we had identified Egr-2 and Egr-3 as NF-AT-induced transcription factors which promote the inhibition of T cell activation. In this report we identify Sprouty1 as a downstream target of Egr-3. CD4<sup>+</sup> T cells lacking Spry1 demonstrate enhanced proliferation and cytokine production. Likewise, Spry1<sup>Flox/Flox</sup> Lck Cre CD8<sup>+</sup> T cells display increased cytolytic activity. Mechanistically, Spry1 acts at the level of PLC-γ promoting the inhibition of both Ca<sup>++</sup> induced NF-AT activation and MAP-kinase induced AP-1 activation while sparing NF-κB signaling. <em>In vivo</em>, mice in which Spry1 is selectively deleted in T cells demonstrate enhanced responses to a tumor vaccine and subsequently reject tumors more robustly than Wt mice. These findings suggest that targeting Spry1 might prove to be a novel means of enhancing tumor immunotherapy.</p> </div>", "links"=>[], "tags"=>["effector", "responses", "sprouty-1"], "article_id"=>117176, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049801.s001", "https://dx.doi.org/10.1371/journal.pone.0049801.s002", "https://dx.doi.org/10.1371/journal.pone.0049801.s003"], "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Regulation_of_CD4_and_CD8_Effector_Responses_by_Sprouty_1__/117176", "title"=>"Regulation of CD4<sup>+</sup> and CD8<sup>+</sup> Effector Responses by Sprouty-1", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-11-15 01:59:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/542599"], "description"=>"<p>B6 Lck Cre mice were crossed to Spry1 flox mice and thymuses (<b>A</b>) and spleens (<b>B</b>) were analyzed for CD4 and CD8 percentages by flow cytometry. <b>C.</b> Grapical representation of thymus and spleen CD4<sup>+</sup> and CD8<sup>+</sup> T cell percentages from wild type and Spry1<sup>Flox/Flox</sup> Lck cre mice. <b>D.</b> Graphical representation of splenic cell numbers of wild type and Spry1<sup>Flox/Flox</sup> Lck cre mice. Error bars represent one standard deviation of the mean. All experiments were performed at least three times. Data are representative of 5 mice per group.</p>", "links"=>[], "tags"=>["spry1", "cells"], "article_id"=>213089, "categories"=>["Cancer", "Immunology"], "users"=>["Sam Collins", "Adam Waickman", "Albert Basson", "Abraham Kupfer", "Jonathan D. Licht", "Maureen R. Horton", "Jonathan D. Powell"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049801.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Loss_of_Spry1_in_CD4_and_CD8_T_cells_does_not_affect_T_cell_development_/213089", "title"=>"Loss of Spry1 in CD4<sup>+</sup> and CD8<sup>+</sup> T cells does not affect T cell development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:51:29"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}

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/Biochemistry", "average_usage"=>[316, 541, 663, 766, 856, 950, 1041, 1128, 1218, 1302, 1382, 1456, 1526, 1593, 1657, 1729, 1796, 1862, 1930, 1999, 2065, 2132, 2202, 2261, 2319]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[313, 562, 690, 796, 893, 986, 1079, 1173, 1257, 1349, 1429, 1506, 1586, 1661, 1730, 1803, 1876, 1945, 2017, 2091, 2163, 2225, 2294, 2362, 2430]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[307, 536, 653, 753, 839, 926, 1017, 1103, 1189, 1268, 1348, 1425, 1492, 1557, 1620, 1686, 1759, 1825, 1891, 1950, 2014, 2079, 2141, 2200, 2255]}, {"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]}]}
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