Agonistic Anti-TIGIT Treatment Inhibits T Cell Responses in LDLr Deficient Mice without Affecting Atherosclerotic Lesion Development
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{"title"=>"Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development", "type"=>"journal", "authors"=>[{"first_name"=>"Amanda C.", "last_name"=>"Foks", "scopus_author_id"=>"36128599400"}, {"first_name"=>"Ingrid A.", "last_name"=>"Ran", "scopus_author_id"=>"55916684400"}, {"first_name"=>"Vanessa", "last_name"=>"Frodermann", "scopus_author_id"=>"48761139700"}, {"first_name"=>"Ilze", "last_name"=>"Bot", "scopus_author_id"=>"35569879300"}, {"first_name"=>"Peter J.", "last_name"=>"Van Santbrink", "scopus_author_id"=>"6507818560"}, {"first_name"=>"Johan", "last_name"=>"Kuiper", "scopus_author_id"=>"7103324153"}, {"first_name"=>"Gijs H M", "last_name"=>"Van Puijvelde", "scopus_author_id"=>"15049967100"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24376654", "doi"=>"10.1371/journal.pone.0083134", "sgr"=>"84893410091", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84893410091", "issn"=>"19326203", "pui"=>"372245343"}, "id"=>"4740adbf-cab9-39ab-be17-13849dcc17ab", "abstract"=>"OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT) directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis.\\n\\nMETHODS AND RESULTS: TIGIT was upregulated on CD4(+) T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/-) mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production.\\n\\nCONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.", "link"=>"http://www.mendeley.com/research/agonistic-antitigit-treatment-inhibits-t-cell-responses-ldlr-deficient-mice-without-affecting-athero", "reader_count"=>47, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Student > Doctoral Student"=>3, "Researcher"=>19, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>4, "Student > Master"=>5, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Student > Doctoral Student"=>3, "Researcher"=>19, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>4, "Student > Master"=>5, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>25, "Medicine and Dentistry"=>7, "Immunology and Microbiology"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>25}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>6}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1324516"], "description"=>"<p>Splenocytes from Western-type diet fed mice (n = 3) were cultured for 72 hours with αCD3/αCD28 in the presence or absence of agonistic anti-TIGIT (0–30 µg/ml). Activated T cells (CD4<sup>+</sup>CD25<sup>+</sup>) were determined with flow cytometry (A). Proliferation was assessed by the amount of <sup>3</sup>H-thymidine incorporation in dividing cells and is expressed as stimulation index (B) and by the amount of IL-2 produced by the splenocytes as determined with ELISA (C). Splenocytes of PBS, Armenian Hamster IgG and agonistic anti-TIGIT-treated mice (n = 5 per group) were cultured in the presence of αCD3/αCD28 stimulation and proliferation was assessed by the amount of 3H-thymidine incorporation expressed as stimulation index (D). *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001.</p>", "links"=>[], "tags"=>["anti-tigit", "inhibits"], "article_id"=>883473, "categories"=>["Biological Sciences"], "users"=>["Amanda C. Foks", "Ingrid A. Ran", "Vanessa Frodermann", "Ilze Bot", "Peter J. van Santbrink", "Johan Kuiper", "Gijs H. M. van Puijvelde"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083134.g002", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Agonistic_anti_TIGIT_strongly_inhibits_T_cell_function_/883473", "title"=>"Agonistic anti-TIGIT strongly inhibits T cell function.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-20 03:23:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1324537", "https://ndownloader.figshare.com/files/1324538"], "description"=>"<div><p>Objective</p><p>Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT) directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis.</p><p>Methods and Results</p><p>TIGIT was upregulated on CD4<sup>+</sup> T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both <i>in vitro</i> and <i>in vivo</i>. However, agonistic anti-TIGIT treatment of LDLr<sup>−/−</sup> mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production.</p><p>Conclusions</p><p>Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.</p></div>", "links"=>[], "tags"=>["anti-tigit", "inhibits", "responses", "ldlr", "deficient", "mice", "affecting", "atherosclerotic", "lesion"], "article_id"=>883490, "categories"=>["Biological Sciences"], "users"=>["Amanda C. Foks", "Ingrid A. Ran", "Vanessa Frodermann", "Ilze Bot", "Peter J. van Santbrink", "Johan Kuiper", "Gijs H. M. van Puijvelde"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083134.s001", "https://dx.doi.org/10.1371/journal.pone.0083134.s002"], "stats"=>{"downloads"=>1, "page_views"=>34, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Agonistic_Anti_TIGIT_Treatment_Inhibits_T_Cell_Responses_in_LDLr_Deficient_Mice_without_Affecting_Atherosclerotic_Lesion_Development_/883490", "title"=>"Agonistic Anti-TIGIT Treatment Inhibits T Cell Responses in LDLr Deficient Mice without Affecting Atherosclerotic Lesion Development", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-12-20 03:23:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1324524"], "description"=>"<p>No difference in atherosclerotic lesion size between agonistic anti-TIGIT, Armenian Hamster IgG and PBS treated LDLr<sup>−/−</sup> mice fed a Western-type diet for 4 weeks. Representative cross-sections of lesion formation in the three valves area of the aortic root stained with Oil-Red-O and hematoxylin are shown and lesion size was determined (A). Sections of the aortic root were stained for collagen using Masson’s trichrome staining. The percentage of collagen relative to the lesion size was determined (B). Furthermore, relative macrophage content was determined with a Moma-2 staining and quantified (C).</p>", "links"=>[], "tags"=>["anti-tigit", "atherosclerotic", "lesion"], "article_id"=>883477, "categories"=>["Biological Sciences"], "users"=>["Amanda C. Foks", "Ingrid A. Ran", "Vanessa Frodermann", "Ilze Bot", "Peter J. van Santbrink", "Johan Kuiper", "Gijs H. M. van Puijvelde"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083134.g003", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Agonistic_anti_TIGIT_treatment_does_not_reduce_initial_atherosclerotic_lesion_development_/883477", "title"=>"Agonistic anti-TIGIT treatment does not reduce initial atherosclerotic lesion development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-20 03:23:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1324525"], "description"=>"<p>At sacrifice, blood (A) and spleen (B) cells were isolated and stained for dendritic cells and activation markers and analyzed by flow cytometry (n = 5 per group). The effect of agonistic anti-TIGIT on IL-10 expression by DCs was determined by culturing splenocytes with increasing concentrations of agonistic anti-TIGIT (C). *<i>P</i><0.05, **<i>P</i><0.01.</p>", "links"=>[], "tags"=>["dendritic", "percentages", "activation", "il-10", "expressing", "cells", "agonistic", "anti-tigit"], "article_id"=>883478, "categories"=>["Biological Sciences"], "users"=>["Amanda C. Foks", "Ingrid A. Ran", "Vanessa Frodermann", "Ilze Bot", "Peter J. van Santbrink", "Johan Kuiper", "Gijs H. M. van Puijvelde"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083134.g004", "stats"=>{"downloads"=>4, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Enhanced_dendritic_cell_percentages_and_activation_and_decreased_IL_10_expressing_dendritic_cells_after_agonistic_anti_TIGIT_treatment_/883478", "title"=>"Enhanced dendritic cell percentages and activation and decreased IL-10 expressing dendritic cells after agonistic anti-TIGIT treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-20 03:23:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1324532"], "description"=>"<p>Agonistic anti-TIGIT treatment (n = 12) and Armenian Hamster IgG treatment (n = 11) reduces atherosclerosis development in LDLr<sup>−/−</sup> mice fed a Western-type diet for 8 weeks in comparison with PBS treatment (n = 12). Representative cross-sections of lesion formation in the three valves area of the aortic root stained with Oil-Red-O and hematoxylin are shown and lesion size was determined (A). Sections of the aortic root were stained for collagen using Masson’s trichrome staining. The percentage of collagen relative to the lesion size was determined (B). Furthermore, relative macrophage content was determined with a Moma-2 staining and quantified (C).</p>", "links"=>[], "tags"=>["anti-tigit"], "article_id"=>883485, "categories"=>["Biological Sciences"], "users"=>["Amanda C. Foks", "Ingrid A. Ran", "Vanessa Frodermann", "Ilze Bot", "Peter J. van Santbrink", "Johan Kuiper", "Gijs H. M. van Puijvelde"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083134.g005", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Agonistic_anti_TIGIT_treatment_does_not_reduce_more_advanced_atherosclerosis_/883485", "title"=>"Agonistic anti-TIGIT treatment does not reduce more advanced atherosclerosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-20 03:23:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1324513"], "description"=>"<p>Representative FACS dot plots of TIGIT surface expression on CD4<sup>+</sup> T cells isolated from LDLr<sup>−/−</sup> mice fed a Chow diet or a Western-type (WT) diet (A). Splenocytes from LDLr<sup>−/−</sup> mice fed a Chow diet (n = 3) and Western-type diet (n = 3) were cultured for 48 hours in the presence or absence of anti-CD3/anti-CD28. Representative dot plots (B) and the mean percentage of TIGIT expressing CD4<sup>+</sup> T cells in 4 different conditions (C) were obtained by flow cytometry. *<i>P</i><0.05.</p>", "links"=>[], "tags"=>["tigit", "cells", "hypercholesterolemic"], "article_id"=>883470, "categories"=>["Biological Sciences"], "users"=>["Amanda C. Foks", "Ingrid A. Ran", "Vanessa Frodermann", "Ilze Bot", "Peter J. van Santbrink", "Johan Kuiper", "Gijs H. M. van Puijvelde"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083134.g001", "stats"=>{"downloads"=>3, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Upregulation_of_TIGIT_expression_on_CD4_T_cells_under_hypercholesterolemic_conditions_/883470", "title"=>"Upregulation of TIGIT expression on CD4<sup>+</sup> T cells under hypercholesterolemic conditions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-20 03:23:15"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"15", "full-text"=>"20", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[266, 466, 591, 701, 799, 887, 982, 1067, 1155, 1237, 1317, 1395, 1458]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[281, 484, 611, 728, 835, 934, 1030, 1123, 1214, 1299, 1383, 1464]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Immunology", "average_usage"=>[262, 463, 587, 693, 790, 882, 965, 1051, 1135, 1218, 1300, 1376, 1438]}, {"subject_area"=>"/Medicine and health sciences/Nutrition", "average_usage"=>[273, 476, 611, 714, 821, 911, 1005, 1103, 1201, 1287, 1388, 1478, 1557]}, {"subject_area"=>"/People and places", "average_usage"=>[270, 456, 573, 676, 773, 867, 955, 1037, 1120, 1205, 1286, 1363, 1436]}]}
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