Self-Organized Criticality Theory of Autoimmunity
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{"title"=>"Self-organized criticality theory of autoimmunity", "type"=>"journal", "authors"=>[{"first_name"=>"Ken", "last_name"=>"Tsumiyama", "scopus_author_id"=>"18038764300"}, {"first_name"=>"Yumi", "last_name"=>"Miyazaki", "scopus_author_id"=>"35748695100"}, {"first_name"=>"Shunichi", "last_name"=>"Shiozawa", "scopus_author_id"=>"7006552995"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0008382", "pui"=>"359097531", "sgr"=>"77954171663", "scopus"=>"2-s2.0-77954171663", "pmid"=>"20046868", "issn"=>"19326203"}, "id"=>"64466533-7023-369e-8e75-a32d3d3ff58a", "abstract"=>"BACKGROUND: The cause of autoimmunity, which is unknown, is investigated from a different angle, i.e., the defect in immune 'system', to explain the cause of autoimmunity. METHODOLOGY/PRINCIPAL FINDINGS: Repeated immunization with antigen causes systemic autoimmunity in mice otherwise not prone to spontaneous autoimmune diseases. Overstimulation of CD4(+) T cells led to the development of autoantibody-inducing CD4(+) T (aiCD4(+) T) cell which had undergone T cell receptor (TCR) revision and was capable of inducing autoantibodies. The aiCD4(+) T cell was induced by de novo TCR revision but not by cross-reaction, and subsequently overstimulated CD8(+) T cells, driving them to become antigen-specific cytotoxic T lymphocytes (CTL). These CTLs could be further matured by antigen cross-presentation, after which they caused autoimmune tissue injury akin to systemic lupus erythematosus (SLE). CONCLUSIONS/SIGNIFICANCE: Systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host's immune 'system' by repeated immunization with antigen, to the levels that surpass system's self-organized criticality.", "link"=>"http://www.mendeley.com/research/selforganized-criticality-theory-autoimmunity", "reader_count"=>43, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Librarian"=>2, "Researcher"=>11, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>4, "Student > Master"=>4, "Other"=>6, "Student > Bachelor"=>5, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Librarian"=>2, "Researcher"=>11, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>4, "Student > Master"=>4, "Other"=>6, "Student > Bachelor"=>5, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>14, "Arts and Humanities"=>1, "Business, Management and Accounting"=>1, "Chemistry"=>2, "Computer Science"=>2, "Earth and Planetary Sciences"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Nursing and Health Professions"=>2, "Medicine and Dentistry"=>15, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Computer Science"=>{"Computer Science"=>2}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"Canada"=>2, "Colombia"=>1, "United States"=>2, "Japan"=>1, "Brazil"=>1, "United Kingdom"=>2}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/869725"], "description"=>"<p>BALB/c mice were repeatedly injected i.p. with 25 µg SEB, 500 µg OVA or PBS every 5 d. (A) Serum IgG- and IgM-RFs, anti-galactose-deficient IgG and anti-Sm antibodies were measured using ELISA. The arbitrary unit (AU) of 1.0 is equivalent to the titer obtained from sera of prototypic autoimmune MRL/lpr mice. Data from each mouse are connected by dotted lines. (B) Adoptive transfer of splenic B, T, CD4<sup>+</sup> T or CD8<sup>+</sup> T cells of SEB-, OVA- or PBS-immunized BALB/c mice into naïve BALB/c mice. The recipient mice were given single i.p. injection of 25 µg SEB or 500 µg OVA 24 h after cell transfer, and autoantibodies were measured 2 weeks later. (C) Adoptive transfer of cells from OVA-immunized BALB/c mice into β<sub>2</sub>m-deficient mice.</p>", "links"=>[], "tags"=>["autoantibodies"], "article_id"=>540184, "categories"=>["Immunology", "Medicine"], "users"=>["Ken Tsumiyama", "Yumi Miyazaki", "Shunichi Shiozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008382.g001", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_autoantibodies_and_proteinuria_/540184", "title"=>"Induction of autoantibodies and proteinuria.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-31 00:03:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/870178"], "description"=>"<p>(A) Spleen cells stimulated with 50 ng/ml phorbol myristate acetate (PMA) and 500 ng/ml ionomycin for 4 h in the presence of brefeldin A (10 µg/ml) and stained for intracellular IFNγ (upper). Subsets of CD8<sup>+</sup> T cells categorized into naïve (CD44<sup>low</sup>CD62L<sup>high</sup>), effector (CD44<sup>high</sup>CD62L<sup>low</sup>), and memory (CD44<sup>high</sup>CD62L<sup>high</sup>) fractions (middle). Flow cytometry of IFNγ<sup>+</sup> cells within naïve or effector/memory CD8<sup>+</sup> T cell populations. Spleen cells were separated into naïve (CD44<sup>low</sup>) and effector/memory (CD44<sup>high</sup>) cells using CD44 MACS beads, and IFNγ<sup>+</sup> cells within the CD8<sup>+</sup> T population was evaluated (lower). (B) Adoptive transfer of splenocytes of OVA-immunized BALB/c mice into naïve recipients. The recipients were injected with 500 µg OVA 24 h after cell transfer, and proteinuria examined 2 weeks later. (C) Cross-presentation of OVA to CD8<sup>+</sup> T cells. Splenic CD11c<sup>+</sup> DC from OVA-immunized or control mice were incubated in the presence (OVA(+)) or absence (OVA(−)) of 1 mg/ml OVA with or without chloroquine (CQ) (20 µg/ml) for 3 h, followed by a co-culture with KJ1-26<sup>+</sup>CD8<sup>+</sup> T cells of DO11.10 transgenic mice for 24 h to examine surface expression of CD69 (upper). Inhibition of cross-presentation <i>in vivo</i> by administration of 250 µg CQ per mouse 3 h prior to immunization with OVA or PBS. IFNγ<sup>+</sup>CD8<sup>+</sup> T cells (middle), autoantibodies and proteinuria (lower) after 12× immunization. (D) Requirement of autoantibody-inducing CD4<sup>+</sup> T cells for CD8<sup>+</sup> T cell-mediated autoimmune tissue injury. BALB/c mice were immunized 12× with KLH, and CD4<sup>+</sup> T cells were isolated using MACS beads. Cells were transferred into the anti-CD4 antibody-treated recipient mice immunized 8× with OVA. Percent matured CTL, i.e., IFNγ<sup>+</sup>CD8<sup>+</sup> T cells, and proteinuria were measured 2 weeks after booster immunization 1× with KLH.</p>", "links"=>[], "tags"=>["cells", "antigen"], "article_id"=>540639, "categories"=>["Immunology", "Medicine"], "users"=>["Ken Tsumiyama", "Yumi Miyazaki", "Shunichi Shiozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008382.g004", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expansion_of_CD8_T_cells_and_antigen_cross_presentation_/540639", "title"=>"Expansion of CD8<sup>+</sup> T cells and antigen cross-presentation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-31 00:10:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/870047"], "description"=>"<p>BALB/c mice were injected i.p. with 500 µg OVA every 5 d. (A) Serum IC measured 2 d after final immunization, expressed as AU. Proteinuria assessed 9 d after final immunization: grades 1, 2 and 3 represent 30–100 mg/dl, 100–300 mg/dl and 300–1000 mg/dl of urinary protein, respectively (upper left). Representative histopathology of kidneys from mice immunized 12× with PBS or OVA (lower left) (H&E staining, bar  = 20 µm; original magnification ×400): glomerular expansion with cellular infiltration including eosinophils seen under the same magnification. Immunohistochemistry for deposited IC, IgG, C3 and OVA (upper right) (bar  = 50 µm; original magnification ×200), and cells infiltrated into glomeruli (bar  = 20 µm; original magnification ×300), stained in serial tissue sections using anti-CD8α (53–6.7) and anti-IFNγ (R4-6A2) monoclonal antibodies, in the specimens of mice immunized 12× with OVA (lower right). (B) Lupus band test stained with anti-IgG and anti-C3 antibodies (bar  = 20 µm; original magnification ×400).</p>", "links"=>[], "tags"=>["autoimmune"], "article_id"=>540507, "categories"=>["Immunology", "Medicine"], "users"=>["Ken Tsumiyama", "Yumi Miyazaki", "Shunichi Shiozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008382.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_autoimmune_tissue_injury_/540507", "title"=>"Induction of autoimmune tissue injury.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-31 00:08:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/431849", "https://ndownloader.figshare.com/files/431943", "https://ndownloader.figshare.com/files/432015", "https://ndownloader.figshare.com/files/432083", "https://ndownloader.figshare.com/files/432128", "https://ndownloader.figshare.com/files/432211", "https://ndownloader.figshare.com/files/432289", "https://ndownloader.figshare.com/files/432331", "https://ndownloader.figshare.com/files/432377"], "description"=>"<div><h3>Background</h3><p>The cause of autoimmunity, which is unknown, is investigated from a different angle, i.e., the defect in immune ‘system’, to explain the cause of autoimmunity.</p><h3>Methodology/Principal Findings</h3><p>Repeated immunization with antigen causes systemic autoimmunity in mice otherwise not prone to spontaneous autoimmune diseases. Overstimulation of CD4<sup>+</sup> T cells led to the development of autoantibody-inducing CD4<sup>+</sup> T (<em>ai</em>CD4<sup>+</sup> T) cell which had undergone T cell receptor (TCR) revision and was capable of inducing autoantibodies. The <em>ai</em>CD4<sup>+</sup> T cell was induced by <em>de novo</em> TCR revision but not by cross-reaction, and subsequently overstimulated CD8<sup>+</sup> T cells, driving them to become antigen-specific cytotoxic T lymphocytes (CTL). These CTLs could be further matured by antigen cross-presentation, after which they caused autoimmune tissue injury akin to systemic lupus erythematosus (SLE).</p><h3>Conclusions/Significance</h3><p>Systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host's immune ‘system’ by repeated immunization with antigen, to the levels that surpass system's self-organized criticality.</p></div>", "links"=>[], "tags"=>["self-organized", "criticality", "autoimmunity"], "article_id"=>145249, "categories"=>["Immunology", "Medicine"], "users"=>["Ken Tsumiyama", "Yumi Miyazaki", "Shunichi Shiozawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008382.s001", "https://dx.doi.org/10.1371/journal.pone.0008382.s002", "https://dx.doi.org/10.1371/journal.pone.0008382.s003", "https://dx.doi.org/10.1371/journal.pone.0008382.s004", "https://dx.doi.org/10.1371/journal.pone.0008382.s005", "https://dx.doi.org/10.1371/journal.pone.0008382.s006", "https://dx.doi.org/10.1371/journal.pone.0008382.s007", "https://dx.doi.org/10.1371/journal.pone.0008382.s008", "https://dx.doi.org/10.1371/journal.pone.0008382.s009"], "stats"=>{"downloads"=>8, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Self_Organized_Criticality_Theory_of_Autoimmunity/145249", "title"=>"Self-Organized Criticality Theory of Autoimmunity", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-12-31 01:27:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/869871"], "description"=>"<p>(A) TCR CDR3 length profiles of mice immunized 8× with PBS, 2× or 8× with SEB. TCR repertoire of splenic CD4<sup>+</sup> T cell was skewed only after immunization 8× with SEB. (B) Expression of V(D)J recombinase complex and related molecules in the spleen of PBS- or SEB-injected BALB/c mice. (C) GFP<sup>+</sup> cells in the Vβ8<sup>+</sup>CD4<sup>+</sup> T population of <i>rag1/gfp</i> knock-in mice. IgG-RF as induced in <i>rag1/gfp</i> knock-in mice after immunization 8× with SEB (lower left). The GFP<sup>+</sup> T cell fraction was also increased among Vβ8<sup>+</sup>CD4<sup>+</sup> T cells (mean ± SD, 4–5 mice/group). (D) TCRα chain revision in the spleen of mice immunized 8× with SEB was determined by LM-PCR detection of dsDNA breaks at the RSS flanking the <i>TCRAV2</i>, with PCR-amplified TCRα constant region (<i>TCRAC</i>) as a DNA quality control.</p>", "links"=>[], "tags"=>["revision", "repeated", "immunization"], "article_id"=>540329, "categories"=>["Immunology", "Medicine"], "users"=>["Ken Tsumiyama", "Yumi Miyazaki", "Shunichi Shiozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008382.g002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TCR_revision_upon_repeated_immunization_with_antigen_/540329", "title"=>"TCR revision upon repeated immunization with antigen.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-31 00:05:29"}

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