{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:27:56Z","timestamp":1772782076621,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T00:00:00Z","timestamp":1261958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epidermolysis bullosa acquisita is a prototypical organ-specific autoimmune disease caused by autoantibodies against type VII collagen of the dermal-epidermal junction. Although mechanisms of autoantibody-induced blister formation were extensively characterized, the initiation of autoantibody production in autoimmune blistering diseases is still poorly defined. In the current study, we addressed the role of T cells for the production of blister-inducing autoantibodies in mice immunized with type VII collagen. To detect autoreactive type VII collagen-specific T cells, lymph node cells from immunized SJL mice were stimulated in vitro with recombinant Ag, and their proliferation was measured by radioactive thymidine incorporation and flow cytometry analysis of CFSE-labeled cells. Interestingly, using synthetic peptides of the immunogen, partly different T and B cell epitopes in mice immunized with type VII collagen were demonstrated. In contrast to wild-type mice, immunization with type VII collagen of SJL athymic nude mice lacking T cells did not induce an autoimmune response and blistering phenotype. Importantly, SJL nude mice repleted with T cells from immunized wild-type mice showed a robust and durable autoantibody production resulting in subepidermal blistering disease in the recipients. Our present results demonstrate that T cells are required for the initiation of autoimmunity against type VII collagen in experimental epidermolysis bullosa acquisita and provide a basis for developing T cell-directed immunomodulatory strategies for this and related autoimmune diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.0901412","type":"journal-article","created":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T20:54:30Z","timestamp":1262033670000},"page":"1596-1603","source":"Crossref","is-referenced-by-count":48,"title":["T Cells Are Required for the Production of Blister-Inducing Autoantibodies in Experimental Epidermolysis Bullosa Acquisita"],"prefix":"10.1093","volume":"184","author":[{"given":"Ana Gabriela","family":"Sitaru","sequence":"first","affiliation":[{"name":"Institute for Medical Microbiology and Hygiene"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Sesarman","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , L\u00fcbeck"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidonia","family":"Mihai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , L\u00fcbeck"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mircea T","family":"Chiriac","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , L\u00fcbeck"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Detlef","family":"Zillikens","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , L\u00fcbeck"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Hultman","sequence":"additional","affiliation":[{"name":"Molecular and Immunological Pathology, Department of Clinical and Experimental Medicine, Link\u00f6ping University , Link\u00f6ping,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Solbach","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hygiene"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassian","family":"Sitaru","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , L\u00fcbeck"},{"name":"Department of Dermatology, University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,28]]},"reference":[{"key":"2026012808090565600_r1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1582-4934.2007.00033.x","article-title":"Immunopathology and molecular diagnosis of autoimmune bullous diseases.","volume":"11","author":"Mihai","year":"2007","journal-title":"J. Cell. Mol. Med."},{"key":"2026012808090565600_r2","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/j.1600-0625.2007.00564.x","article-title":"Experimental models of epidermolysis bullosa acquisita.","volume":"16","author":"Sitaru","year":"2007","journal-title":"Exp. Dermatol."},{"key":"2026012808090565600_r3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0002-9440(10)64182-X","article-title":"Autoantibodies to type VII collagen mediate Fcgamma-dependent neutrophil activation and induce dermal-epidermal separation in cryosections of human skin.","volume":"161","author":"Sitaru","year":"2002","journal-title":"Am. J. Pathol."},{"key":"2026012808090565600_r4","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1172\/JCI200521386","article-title":"Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen.","volume":"115","author":"Sitaru","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2026012808090565600_r5","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.4049\/jimmunol.177.5.3461","article-title":"Induction of complement-fixing autoantibodies against type VII collagen results in subepidermal blistering in mice.","volume":"177","author":"Sitaru","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808090565600_r6","first-page":"S67","article-title":"T and B cell responses targeting distinct regions of the non-collagenous domain (NC) 1 domain of type VII collagen correlate with the clinical activity","volume":"127","author":"M\u00fcller","year":"2007","journal-title":"J. Invest. Dermatol."},{"key":"2026012808090565600_r7","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/path.2157","article-title":"NADPH oxidase is required for neutrophil-dependent autoantibody-induced tissue damage.","volume":"212","author":"Chiriac","year":"2007","journal-title":"J. Pathol."},{"key":"2026012808090565600_r8","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/j.1600-0625.2005.00367.x","article-title":"Mechanisms of blister induction by autoantibodies.","volume":"14","author":"Sitaru","year":"2005","journal-title":"Exp. Dermatol."},{"key":"2026012808090565600_r9","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.4049\/jimmunol.149.9.3083","article-title":"Development of murine lupus in CD4-depleted NZB\/NZW mice. Sustained inhibition of residual CD4+ T cells is required to suppress autoimmunity.","volume":"149","author":"Connolly","year":"1992","journal-title":"J. Immunol."},{"key":"2026012808090565600_r10","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1073\/pnas.80.9.2713","article-title":"In vivo therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor.","volume":"80","author":"Waldor","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026012808090565600_r11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1084\/jem.184.2.349","article-title":"Both CD4+ and CD8+ T cells are essential to induce experimental autoimmune myasthenia gravis.","volume":"184","author":"Zhang","year":"1996","journal-title":"J. Exp. Med."},{"key":"2026012808090565600_r12","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1172\/JCI119764","article-title":"Susceptibility to anti-glomerular basement membrane disease and Goodpasture syndrome is linked to MHC class II genes and the emergence of T cell-mediated immunity in mice.","volume":"100","author":"Kalluri","year":"1997","journal-title":"J. Clin. Invest."},{"key":"2026012808090565600_r13","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.4049\/jimmunol.168.6.2689","article-title":"IL-4 and T cells are required for the generation of IgG1 isotype antibodies against cardiolipin.","volume":"168","author":"Fischer","year":"2002","journal-title":"J. Immunol."},{"key":"2026012808090565600_r14","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.4049\/jimmunol.181.2.1526","article-title":"Novel system evaluating in vivo pathogenicity of desmoglein 3-reactive T cell clones using murine pemphigus vulgaris.","volume":"181","author":"Takahashi","year":"2008","journal-title":"J. Immunol."},{"key":"2026012808090565600_r15","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/1521-4141(200203)32:3<627::AID-IMMU627>3.0.CO;2-1","article-title":"Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris.","volume":"32","author":"Tsunoda","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"2026012808090565600_r16","doi-asserted-by":"crossref","first-page":"3152","DOI":"10.4049\/jimmunol.152.6.3152","article-title":"Major histocompatibility complex class II gene disruption prevents experimental autoimmune myasthenia gravis.","volume":"152","author":"Kaul","year":"1994","journal-title":"J. Immunol."},{"key":"2026012808090565600_r17","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/sj.icb.7100142","article-title":"B cells flying solo.","volume":"86","author":"Groom","year":"2008","journal-title":"Immunol. Cell Biol."},{"key":"2026012808090565600_r18","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1097\/BOR.0b013e328277ef4c","article-title":"An important role for B-cell activation factor and B cells in the pathogenesis of Sj\u00f6gren\u2019s syndrome.","volume":"19","author":"Mackay","year":"2007","journal-title":"Curr. Opin. Rheumatol."},{"key":"2026012808090565600_r19","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.immuni.2008.06.009","article-title":"T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells.","volume":"29","author":"Herlands","year":"2008","journal-title":"Immunity"},{"key":"2026012808090565600_r20","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1006\/clin.1995.1155","article-title":"Genetic susceptibility to silver-induced anti-fibrillarin autoantibodies in mice.","volume":"77","author":"Hultman","year":"1995","journal-title":"Clin. Immunol. Immunopathol."},{"key":"2026012808090565600_r21","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00109-008-0366-7","article-title":"Neonatal Fc receptor deficiency protects from tissue injury in experimental epidermolysis bullosa acquisita.","volume":"86","author":"Sesarman","year":"2008","journal-title":"J. Mol. Med."},{"key":"2026012808090565600_r22","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1365-2133.2007.08388.x","article-title":"Binding of avian IgY to type VII collagen does not activate complement and leucocytes and fails to induce subepidermal blistering in mice.","volume":"158","author":"Sesarman","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"2026012808090565600_r23","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0014-5793(90)80535-Q","article-title":"A semi-empirical method for prediction of antigenic determinants on protein antigens.","volume":"276","author":"Kolaskar","year":"1990","journal-title":"FEBS Lett."},{"key":"2026012808090565600_r24","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/S0168-9525(00)02024-2","article-title":"EMBOSS: the European Molecular Biology Open Software Suite.","volume":"16","author":"Rice","year":"2000","journal-title":"Trends Genet."},{"key":"2026012808090565600_r25","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1160\/TH05-02-0127","article-title":"Chorioamnionitis is associated with increased CD40L expression on cord blood platelets.","volume":"94","author":"Sitaru","year":"2005","journal-title":"Thromb. Haemost."},{"key":"2026012808090565600_r26","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/09537100400016862","article-title":"Neonatal platelets from cord blood and peripheral blood.","volume":"16","author":"Sitaru","year":"2005","journal-title":"Platelets"},{"key":"2026012808090565600_r27","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/path.1674","article-title":"Granulocyte-derived elastase and gelatinase B are required for dermal-epidermal separation induced by autoantibodies from patients with epidermolysis bullosa acquisita and bullous pemphigoid.","volume":"204","author":"Shimanovich","year":"2004","journal-title":"J. Pathol."},{"key":"2026012808090565600_r28","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/S0198-8859(02)00452-4","article-title":"Hierarchical immunogenicity of donor MHC class I peptides in allotransplantation.","volume":"63","author":"Sitaru","year":"2002","journal-title":"Hum. Immunol."},{"key":"2026012808090565600_r29","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.humimm.2004.05.007","article-title":"Allogeneic core amino acids of an immunodominant allopeptide are important for MHC binding and TCR recognition.","volume":"65","author":"Sitaru","year":"2004","journal-title":"Hum. Immunol."},{"key":"2026012808090565600_r30","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1172\/JCI116774","article-title":"Epitope mapping of type VII collagen. Identification of discrete peptide sequences recognized by sera from patients with acquired epidermolysis bullosa.","volume":"92","author":"Lapiere","year":"1993","journal-title":"J. Clin. Invest."},{"key":"2026012808090565600_r31","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1111\/1523-1747.ep12374333","article-title":"Epitope mapping for epidermolysis bullosa acquisita autoantibody by molecularly cloned cDNA for type VII collagen.","volume":"102","author":"Tanaka","year":"1994","journal-title":"J. Invest. Dermatol."},{"key":"2026012808090565600_r32","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1111\/j.0022-202X.2005.23702.x","article-title":"Evidence that anti-type VII collagen antibodies are pathogenic and responsible for the clinical, histological, and immunological features of epidermolysis bullosa acquisita.","volume":"124","author":"Woodley","year":"2005","journal-title":"J. Invest. Dermatol."},{"key":"2026012808090565600_r33","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.2353\/ajpath.2007.061212","article-title":"The cartilage matrix protein subdomain of type VII collagen is pathogenic for epidermolysis bullosa acquisita.","volume":"170","author":"Chen","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2026012808090565600_r34","doi-asserted-by":"crossref","first-page":"7364","DOI":"10.4049\/jimmunol.177.10.7364","article-title":"Epitope specificity of autoreactive T and B cells associated with experimental autoimmune encephalomyelitis and optic neuritis induced by oligodendrocyte-specific protein in SJL\/J mice.","volume":"177","author":"Kaushansky","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808090565600_r35","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.4049\/jimmunol.127.4.1420","article-title":"Adoptive transfer of experimental allergic encephalomyelitis in SJL\/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt 1+ 2- T lymphocytes.","volume":"127","author":"Pettinelli","year":"1981","journal-title":"J. Immunol."},{"key":"2026012808090565600_r36","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/1523-1747.ep12480369","article-title":"The subclass distribution of IgG autoantibodies in cicatricial pemphigoid and epidermolysis bullosa acquisita.","volume":"97","author":"Bernard","year":"1991","journal-title":"J. Invest. Dermatol."},{"key":"2026012808090565600_r37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00403-007-0734-0","article-title":"The relevance of the IgG subclass of autoantibodies for blister induction in autoimmune bullous skin diseases.","volume":"299","author":"Sitaru","year":"2007","journal-title":"Arch. Dermatol. Res."},{"key":"2026012808090565600_r38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1136\/vr.146.7.193","article-title":"Novel localised variant of canine epidermolysis bullosa acquisita.","volume":"146","author":"Olivry","year":"2000","journal-title":"Vet. Rec."},{"key":"2026012808090565600_r39","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1748-5827.2007.00419.x","article-title":"Epidermolysis bullosa acquisita in a Great Dane.","volume":"49","author":"Hill","year":"2008","journal-title":"J. Small Anim. Pract."},{"key":"2026012808090565600_r40","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1354\/vp.36-4-328","article-title":"Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180\/BPAG2).","volume":"36","author":"Olivry","year":"1999","journal-title":"Vet. Pathol."},{"key":"2026012808090565600_r41","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1177\/030098589503200407","article-title":"Canine bullous pemphigoid (BP): identification of the 180-kd canine BP antigen by circulating autoantibodies.","volume":"32","author":"Iwasaki","year":"1995","journal-title":"Vet. Pathol."},{"key":"2026012808090565600_r42","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/PL00007459","article-title":"A spontaneously arising porcine model of bullous pemphigoid.","volume":"292","author":"Olivry","year":"2000","journal-title":"Arch. Dermatol. Res."},{"key":"2026012808090565600_r43","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0165-2427(99)00151-8","article-title":"Equine bullous pemphigoid IgG autoantibodies target linear epitopes in the NC16A ectodomain of collagen XVII (BP180, BPAG2).","volume":"73","author":"Olivry","year":"2000","journal-title":"Vet. Immunol. Immunopathol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/3\/1596\/62715544\/ji_0901412.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/3\/1596\/62715544\/ji_0901412.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:10:00Z","timestamp":1769605800000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/3\/1596\/8013485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,28]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2009,12,28]]},"published-print":{"date-parts":[[2010,2,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0901412","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,2]]},"published":{"date-parts":[[2009,12,28]]}}}