{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:15:20Z","timestamp":1761196520534},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,4,26]],"date-time":"2004-04-26T00:00:00Z","timestamp":1082937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oral Microbiology and Immunology"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:p>Oral spirochetes may contribute to the pathogenesis of a number of disorders including periodontal and periradicular diseases; however, the mechanism (s) by which these organisms act to cause disease is unknown. We have previously shown that extracts of the oral spirochete, <jats:italic>Treponema denticola,<\/jats:italic> contain an immunosuppressive protein (Sip) which impairs human lymphocyte proliferation. The objective of this study was to determine the mechanism by which Sip alters the proliferative response of lymphocytes. Human T\u2010cells were activated by PHA in the presence or absence of Sip and cell cycle progression was assessed by flow cytometry. Cell cycle distribution was based upon DNA, RNA and protein content as well as expression of the activation markers; CD69 and IL\u20102R. Seventy\u2010two hours following activation with PHA, cells were found in the G<jats:sub>0<\/jats:sub>, G<jats:sub>1<\/jats:sub>, S and G<jats:sub>2<\/jats:sub>\/M phases of the cell cycle. In contrast, pretreatment with Sip resulted in a significant reduction of cells in the S and G<jats:sub>2<\/jats:sub>\/M phases and a concomitant increase in the G<jats:sub>1<\/jats:sub> phase. Sip did not alter the expression of the early activation markers CD69 and CD25R. To determine if G<jats:sub>1<\/jats:sub> arrest resulted in activation of the checkpoint and cell death, we also monitored Sip\u2010treated cells for apoptosis. Indeed, treatment with Sip resulted in both DNA fragmentation and caspase activation after 96\u2003h. Our results indicate that Sip induces G<jats:sub>1<\/jats:sub> arrest in human T\u2010cells and, furthermore, that the arrest is irreversible, culminating in activation of the apoptotic cascade. We propose that if cell cycle arrest occurs <jats:italic>in\u2003vivo<\/jats:italic>, it may result in local and\/or systemic immunosuppression and thereby enhance the pathogenicity of spirochetes and\/or that of other opportunistic organisms.<\/jats:p>","DOI":"10.1111\/j.0902-0055.2004.00129.x","type":"journal-article","created":{"date-parts":[[2004,4,26]],"date-time":"2004-04-26T10:29:55Z","timestamp":1082975395000},"page":"144-149","source":"Crossref","is-referenced-by-count":14,"title":["<i>Treponema denticola<\/i> immunoinhibitory protein induces irreversible G<sub>1<\/sub> arrest in activated human lymphocytes"],"prefix":"10.1111","volume":"19","author":[{"given":"W.","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Pankoski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Zekavat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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