{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T03:14:17Z","timestamp":1789528457154,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The objective of this study was to determine the phenotypic profile of blood mononuclear cells, specifically CD8<jats:sup>+<\/jats:sup>\/CD28<jats:sup>+<\/jats:sup> cells, in patients with generalized aggressive periodontitis (GAgP) and chronic periodontitis (CP) in peripheral blood and in blood obtained from periodontal defect site which might contribute to tissue damage. 13\u2005GAgP, 11 chronic periodontitis (CP) and 5 healthy controls (H) were included in the study. Plaque index (PI), bleeding on probing (BoP), periodontal probing depth (PPD) and clinical attachment level (CAL) were recorded. Blood from the base of periodontal defect site and peripheral blood from the antecubital vein were obtained. Relative counts of CD45<jats:sup>+<\/jats:sup>, CD3<jats:sup>+<\/jats:sup>, CD4<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup>\/CD28<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup>\/CD28<jats:sup>\u2212<\/jats:sup>, CD19<jats:sup>+<\/jats:sup>, CD16<jats:sup>+<\/jats:sup>\/CD56<jats:sup>+<\/jats:sup>\/CD3, CD3<jats:sup>+<\/jats:sup>\/CD16<jats:sup>+<\/jats:sup>\/CD56<jats:sup>+<\/jats:sup> receptors were determined with two color flow cytometry using monoclonal antibodies. BoP, PPD and CAL were significantly higher in both periodontitis groups than healthy controls (p &lt;0.05). Activated cytotoxic T cells, CD8<jats:sup>+<\/jats:sup>\/CD28<jats:sup>+<\/jats:sup> cells, were significantly elevated in GAgP and CP groups compared to HC both in blood obtained from defect site and blood obtained from systemic circulation (p &lt;0.05). GAgP and CP patients have an increased levels of activated cytotoxic T cells as a result of inflammation which may cause severe tissue damage that lead to severe and rapid loss of periodontal tissues.<\/jats:p>","DOI":"10.1038\/srep09262","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T10:13:35Z","timestamp":1426760015000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The Role of Activated Cytotoxic T Cells in Etiopathogenesis of Periodontal Disease: Does It Harm or Does It Heal?"],"prefix":"10.1038","volume":"5","author":[{"given":"Emine","family":"Cifcibasi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meral","family":"Ciblak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayram","family":"Kiran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selim","family":"Badur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhan","family":"Firatli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halim","family":"Issever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar","family":"Cintan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,19]]},"reference":[{"key":"BFsrep09262_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","volume":"4","author":"GC Armitage","year":"1999","unstructured":"Armitage, G. C. International workshop for a classification of periodontal diseases and conditions. Ann Periodontol. 4, 1\u2013112 (1999).","journal-title":"Ann Periodontol."},{"key":"BFsrep09262_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1034\/j.1600-0757.2001.22250102.x","volume":"25","author":"FD Kinane","year":"2001","unstructured":"Kinane, F. D. Causation and pathogenesis of periodontal disease. Periodont 2000. 25, 8\u201320 (2001).","journal-title":"Periodont 2000."},{"key":"BFsrep09262_CR3","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1034\/j.1600-051X.1999.260309.x","volume":"26","author":"DF Lappin","year":"1999","unstructured":"Lappin, D. F., Koulouri, O., Radvar, M., Hodge, P. & Kinane, D. F. Relative proportions of mononuclear cell types in periodontal lesions analyzed by immunohistochemistry. J Clin Periodontol. 26, 183\u2013189 (1999).","journal-title":"J Clin Periodontol."},{"key":"BFsrep09262_CR4","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1902\/jop.2001.72.11.1545","volume":"72","author":"RK Liu","year":"2001","unstructured":"Liu, R. K., Cao, C. F., Meng, H. X. & Gao, Y. Polymorphonuclear neutrophils and their mediators in gingival tissues from generalized aggressive periodontitis. J Periodontol. 72, 1545\u20131553 (2001).","journal-title":"J Periodontol."},{"key":"BFsrep09262_CR5","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1111\/j.1600-0765.2006.00869.x","volume":"41","author":"BW Sigusch","year":"2006","unstructured":"Sigusch, B. W., Wutzler, A., Nietzsch, T. & Glockmann, E. Evidence for a specific crevicular lymphocyte profile in aggressive periodontitis. J Periodontal Res. 41, 391\u2013396 (2006).","journal-title":"J Periodontal Res."},{"key":"BFsrep09262_CR6","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1034\/j.1600-051X.2002.290807.x","volume":"29","author":"T Berglund","year":"2000","unstructured":"Berglund, T., Liljenberg, B. & Lindhe, J. Some cytokine profiles of T-helper cells in lesions of advanced periodontitis. J Clin Periodontol. 29, 705\u2013709 (2000).","journal-title":"J Clin Periodontol."},{"key":"BFsrep09262_CR7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.archoralbio.2008.06.014","volume":"54","author":"A Bodineau","year":"2009","unstructured":"Bodineau, A., Coulomb, B., Tedesco, A. C. & S\u00e9guier, S. Increase of gingival matured dendritic cells number in elderly patients with chronic periodontitis. Arch Oral Biol. 54, 12\u201316 (2009).","journal-title":"Arch Oral Biol."},{"key":"BFsrep09262_CR8","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1177\/10454411970080010201","volume":"8","author":"S Murakami","year":"1997","unstructured":"Murakami, S. & Okada, H. Lymphocyte-fibroblast interactions. Crit Rev Oral Biol Med. 8, 40\u201350 (1997).","journal-title":"Crit Rev Oral Biol Med."},{"key":"BFsrep09262_CR9","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/S0003-9969(00)00018-2","volume":"45","author":"S Seguier","year":"2000","unstructured":"Seguier, S., Godeau, G. & Brousse, N. Immunohistological and morphometric analysis of intraepithelial lymphocytes and langerhans cells in healthy and diseased human gingival tissues. Arch Oral Biol. 45, 441\u2013452 (2000).","journal-title":"Arch Oral Biol."},{"key":"BFsrep09262_CR10","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/S0003-9969(00)00018-2","volume":"45","author":"S Seguier","year":"2000","unstructured":"Seguier, S., Godeau, G. & Brousse, N. Immunohistological and morphometric analysis of intraepithelial lymphocytes and langerhans cells in healthy and diseased human gingival tissues. Arch Oral Biol. 45, 441\u2013452 (2000).","journal-title":"Arch Oral Biol."},{"key":"BFsrep09262_CR11","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.1600-0765.1979.tb00216.x","volume":"14","author":"GJ Seymour","year":"1979","unstructured":"Seymour, G. J. & Greenspan, J. S. The phenotypic characterization of lymphocyte subpopulations in established human periodontal disease. J Periodontal Res. 14, 39\u201346 (1979).","journal-title":"J Periodontal Res."},{"key":"BFsrep09262_CR12","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1177\/154405910308200202","volume":"82","author":"TE Van Dyke","year":"2003","unstructured":"Van Dyke, T. E. & Serhan, C. N. Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res. 82, 90\u201314 (2003).","journal-title":"J Dent Res."},{"key":"BFsrep09262_CR13","first-page":"113","volume":"87","author":"A Wassenaar","year":"1996","unstructured":"Wassenaar, A., Reinhardus, C., Abraham-Inpijn, L. & Kievits, F. Type-1 and type-2 CD8+ T-cell subsets isolated from chronic adult periodontitis tissue differ in surface phenotype and biological functions. Immunology. 87, 113\u2013118 (1996).","journal-title":"Immunology."},{"key":"BFsrep09262_CR14","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1902\/jop.1993.64.2.120","volume":"64","author":"H Celenligil","year":"1993","unstructured":"Celenligil, H., Kansu, E., Ruacan, S., Eratalay, K. & Caglayan, G. In situ characterization of gingival mononuclear cells in rapidly progressive periodontitis. J Periodontol. 64, 120\u20137 (1993).","journal-title":"J Periodontol."},{"key":"BFsrep09262_CR15","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1177\/10454411010120020301","volume":"12","author":"MA Taubman","year":"2001","unstructured":"Taubman, M. A. & Kawai, T. Involvement of T-lymphocytes in periodontal disease and in direct and indirect induction of bone resorption. Crit Rev Oral Biol Med. 12, 125\u201335 (2001).","journal-title":"Crit Rev Oral Biol Med."},{"key":"BFsrep09262_CR16","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/j.1600-0757.2006.00173.x","volume":"43","author":"E Gemmell","year":"2007","unstructured":"Gemmell, E., Yamazaki, K. & Seymour, G. J. The role of T cells in periodontal disease: homeostasis and autoimmunity. Periodontol 2000. 43, 14\u201340 (2007).","journal-title":"Periodontol 2000."},{"key":"BFsrep09262_CR17","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1600-0757.2010.00354.x","volume":"53","author":"M Smith","year":"2010","unstructured":"Smith, M., Seymour, G. J. & Cullinan, M. P. Histopathological features of chronic and aggressive periodontitis. Periodontol 2000. 53, 45\u201354 (2010).","journal-title":"Periodontol 2000."},{"key":"BFsrep09262_CR18","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1111\/j.1399-302X.1992.tb00029.x","volume":"7","author":"T Ishii","year":"1992","unstructured":"Ishii, T., Mahanonda, R. & Seymor, G. J. The establishment of human T cell lines reactive with specific periodontal bacteria. Oral Microbiol Immunol. 7, 225\u2013229 (1992).","journal-title":"Oral Microbiol Immunol."},{"key":"BFsrep09262_CR19","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1111\/j.1600-051X.1991.tb02310.x","volume":"18","author":"GJ Seymour","year":"1991","unstructured":"Seymour, G. J. Importance of the host response in the periodontium. J Clin Periodontol. 18, 421\u2013426 (1991).","journal-title":"J Clin Periodontol."},{"key":"BFsrep09262_CR20","first-page":"218","volume":"47","author":"MD Pietruska","year":"2002","unstructured":"Pietruska, M. D., Zimnoch, L., Waszkiel, D., Stokowska, W. & Duraj, E. Evaluation of lymphocyte populations and subpopulations extracted from inflamed periodontal tissues. Rocz Akad Med Bialymst. 47, 218\u2013225 (2002).","journal-title":"Rocz Akad Med Bialymst."},{"key":"BFsrep09262_CR21","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1111\/j.1600-0765.1993.tb01076.x","volume":"28","author":"K Yamazaki","year":"1993","unstructured":"Yamazaki, K., Nakajima, T., Aoyagi, T. & Hara, K. Immunohistological analysis of memory T lymphocytes and activated B lymphocytes in tissues with periodontal disease. J Periodontol Res. 28, 324\u201334 (1993).","journal-title":"J Periodontol Res."},{"key":"BFsrep09262_CR22","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1111\/j.1600-051X.1996.tb01811.x","volume":"23","author":"E Firatli","year":"1996","unstructured":"Firatli, E., G\u00fcrel, N., Efeo\u011flu, A. & Cebeci, I. Generalized prepubertal periodontitis. A report of 4 cases with the immunological findings. J Clin Periodontol. 23, 1104\u201311 (1996).","journal-title":"J Clin Periodontol."},{"key":"BFsrep09262_CR23","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1034\/j.1600-051x.2001.028005419.x","volume":"28","author":"N Buduneli","year":"2001","unstructured":"Buduneli, N., Bi\u00e7ak\u00e7i, N. & Keskino\u011flu, A. Flow-cytometric analysis of lymphocyte subsets and mCD14 expression in patients with various periodontitis categories. J Clin Periodontol. 28, 419\u201324 (2001).","journal-title":"J Clin Periodontol."},{"key":"BFsrep09262_CR24","first-page":"87","volume":"3","author":"G Emingil","year":"2001","unstructured":"Emingil, G., Karaarslan, F., Keskino\u011flu, A., Coker, I. & Atilla, G. Phenotypic and functional analysis of peripheral blood mononuclear cells in generalised aggressive and chronic periodontitis patients. J Int Acad Periodontol. 3, 87\u201394 (2001).","journal-title":"J Int Acad Periodontol."},{"key":"BFsrep09262_CR25","first-page":"1","volume":"23","author":"SP Lad","year":"2007","unstructured":"Lad, S. P., Patil, C. G., Laws, E. R. Jr. & Katznelson, L. The role of inferior petrosal sinus sampling in the diagnostic localization of Cushing's disease. Neurosurg Focus. 23, 1\u20136 (2007).","journal-title":"Neurosurg Focus."},{"key":"BFsrep09262_CR26","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3109\/00016356408993968","volume":"22","author":"J Silness","year":"1964","unstructured":"Silness, J. & Loe, H. Periodontal disease in pregnancy: II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand. 22, 121\u2013135 (1964).","journal-title":"Acta Odontol Scand."},{"key":"BFsrep09262_CR27","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1902\/jop.2004.75.9.1209","volume":"75","author":"LJ Su\u00e1rez","year":"2004","unstructured":"Su\u00e1rez, L. J., Ocampo, A. M., Due\u00f1as, R. E. & Rodr\u00edguez, A. Relative proportions of T-cell subpopulations and cytokines that mediate and regulate the adaptive immune response in patients with aggressive periodontitis. J Periodontol. 75, 1209\u201315 (2004).","journal-title":"J Periodontol."},{"key":"BFsrep09262_CR28","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s00784-009-0374-1","volume":"15","author":"L Artese","year":"2011","unstructured":"Artese, L. et al. Immunohistochemical analysis of inflammatory infiltrate in aggressive and chronic periodontitis: a comparative study. Clin Oral Investig. 15, 233\u201340 (2011).","journal-title":"Clin Oral Investig."},{"key":"BFsrep09262_CR29","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.jaut.2013.06.004","volume":"45","author":"DM Gravano","year":"2013","unstructured":"Gravano, D. M. & Hoyer, K. K. Promotion and prevention of autoimmune disease by CD8+ T cells. J Autoimmun. 45, 68\u201379 (2013).","journal-title":"J Autoimmun."},{"key":"BFsrep09262_CR30","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1111\/j.1600-051X.1990.tb01685.x","volume":"17","author":"GG Zafiropoulos","year":"1990","unstructured":"Zafiropoulos, G. G., Flores-de-Jacoby, L., Schoop, B., Havemann, K. & Heymanns, J. Flow-cytometric analysis of lymphocyte subsets in patients with advanced periodontitis. J Clin Periodontol. 17, 636\u201341 (1990).","journal-title":"J Clin Periodontol."},{"key":"BFsrep09262_CR31","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/j.1600-0765.1992.tb01814.x","volume":"27","author":"B Afar","year":"1992","unstructured":"Afar, B., Engel, D. & Clark, E. A. Activated lymphocyte subsets in adult periodontitis. J Periodontal Res. 27, 126\u201333 (1992).","journal-title":"J Periodontal Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep09262","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep09262.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep09262.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:39:07Z","timestamp":1672965547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep09262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,19]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,8,14]]}},"alternative-id":["BFsrep09262"],"URL":"https:\/\/doi.org\/10.1038\/srep09262","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,19]]},"assertion":[{"value":"26 August 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9262"}}