{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:37:42Z","timestamp":1776062262775,"version":"3.50.1"},"posted":{"date-parts":[[2023,8,3]]},"group-title":"Immunology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                  (CT) is the most common bacterial sexually transmitted infection globally. Understanding natural immunity to CT will inform vaccine design. This study aimed to profile immune cells and associated functional features in CT-infected women, and determine immune profiles associated with reduced risk of ascended endometrial CT infection and CT reinfection. PBMCs from CT-exposed women were profiled by mass cytometry and random forest models identified key features that distinguish outcomes. CT+ participants exhibited higher frequencies of CD4+ Th2, Th17, and Th17 DN CD4 T effector memory (TEM) cells than uninfected participants with decreased expression of T cell activation and differentiation markers. No significant differences were detected between women with or without endometrial CT infection. Participants who remained follow-up negative (FU-) showed higher frequencies of CD4 T central memory (TCM) Th1, Th17, Th1\/17, and Th17 DN but reduced CD4 TEM Th2 cells than FU+ participants. Expression of markers associated with central memory and Th17 lineage were increased on T cell subsets among FU- participants. These data indicate that peripheral T cells exhibit distinct features associated with resistance to CT reinfection. The highly plastic Th17 lineage appears to contribute to protection. Addressing these immune nuances could promote efficacy of CT vaccines.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>GRAPHICAL ABSTRACT<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"551709v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2023.08.02.551709","type":"posted-content","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T02:00:10Z","timestamp":1691114410000},"source":"Crossref","is-referenced-by-count":5,"title":["Unique T cell signatures associated with reduced\n                  <i>Chlamydia trachomatis<\/i>\n                  reinfection in a highly exposed cohort"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7050-0164","authenticated-orcid":false,"given":"Kacy S","family":"Yount","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Jane","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avinash","family":"Kollipara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha V","family":"Mokashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2248-933X","authenticated-orcid":false,"given":"Xiaojing","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C Bruce","family":"Bagwell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5985-4153","authenticated-orcid":false,"given":"Taylor B","family":"Poston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harold C","family":"Wiesenfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon L","family":"Hillier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8229-684X","authenticated-orcid":false,"given":"Catherine M","family":"O\u2019Connell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Stanley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1507-2202","authenticated-orcid":false,"given":"Toni","family":"Darville","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024111223301742000_2023.08.02.551709v2.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143304"},{"key":"2024111223301742000_2023.08.02.551709v2.2","doi-asserted-by":"publisher","DOI":"10.1086\/652395"},{"key":"2024111223301742000_2023.08.02.551709v2.3","doi-asserted-by":"publisher","DOI":"10.1086\/513844"},{"key":"2024111223301742000_2023.08.02.551709v2.4","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31825a6bc9"},{"key":"2024111223301742000_2023.08.02.551709v2.5","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit094"},{"key":"2024111223301742000_2023.08.02.551709v2.6","doi-asserted-by":"publisher","DOI":"10.1086\/648734"},{"key":"2024111223301742000_2023.08.02.551709v2.7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1998.00549.x"},{"key":"2024111223301742000_2023.08.02.551709v2.8","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.63.12.4661-4668.1995"},{"issue":"6","key":"2024111223301742000_2023.08.02.551709v2.9","first-page":"305","article-title":"Chlamydia trachomatis pneumonia in the severe combined immunodeficiency (SCID) mouse","volume":"5","year":"1993","journal-title":"Reg Immunol"},{"key":"2024111223301742000_2023.08.02.551709v2.10","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.65.6.1993-1999.1997"},{"key":"2024111223301742000_2023.08.02.551709v2.11","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.12.6979-6987.2000"},{"key":"2024111223301742000_2023.08.02.551709v2.12","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.62.9.3705-3711.1994"},{"key":"2024111223301742000_2023.08.02.551709v2.13","doi-asserted-by":"publisher","DOI":"10.1086\/652399"},{"key":"2024111223301742000_2023.08.02.551709v2.14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.7.3344"},{"key":"2024111223301742000_2023.08.02.551709v2.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa8205"},{"key":"2024111223301742000_2023.08.02.551709v2.16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010333"},{"key":"2024111223301742000_2023.08.02.551709v2.17","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.11.5457-5461.1998"},{"key":"2024111223301742000_2023.08.02.551709v2.18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700914"},{"key":"2024111223301742000_2023.08.02.551709v2.19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011914"},{"key":"2024111223301742000_2023.08.02.551709v2.20","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00984-10"},{"key":"2024111223301742000_2023.08.02.551709v2.21","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv438"},{"key":"2024111223301742000_2023.08.02.551709v2.22","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw485"},{"key":"2024111223301742000_2023.08.02.551709v2.23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01981"},{"key":"2024111223301742000_2023.08.02.551709v2.24","doi-asserted-by":"crossref","unstructured":"Zhong W , Kollipara A , Liu Y , Wang Y , O\u2019Connell CM , Poston TB , et al. Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity. Front Immunol. 2022;13:1001255.","DOI":"10.3389\/fimmu.2022.1001255"},{"key":"2024111223301742000_2023.08.02.551709v2.25","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13103"},{"key":"2024111223301742000_2023.08.02.551709v2.26","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab496"},{"key":"2024111223301742000_2023.08.02.551709v2.27","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23724"},{"key":"2024111223301742000_2023.08.02.551709v2.28","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.1.129"},{"key":"2024111223301742000_2023.08.02.551709v2.29","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-016-0293-6"},{"key":"2024111223301742000_2023.08.02.551709v2.30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.1.214"},{"key":"2024111223301742000_2023.08.02.551709v2.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.04.010"},{"key":"2024111223301742000_2023.08.02.551709v2.32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-378653"},{"key":"2024111223301742000_2023.08.02.551709v2.33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600737"},{"key":"2024111223301742000_2023.08.02.551709v2.34","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.100"},{"key":"2024111223301742000_2023.08.02.551709v2.35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302734"},{"key":"2024111223301742000_2023.08.02.551709v2.36","doi-asserted-by":"publisher","DOI":"10.1038\/ni1467"},{"key":"2024111223301742000_2023.08.02.551709v2.37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-213"},{"key":"2024111223301742000_2023.08.02.551709v2.38","doi-asserted-by":"crossref","unstructured":"Rahman KS , Darville T , Russell AN , O\u2019Connell CM , Wiesenfeld HC , Hillier SL , et al. Comprehensive Molecular Serology of Human Chlamydia trachomatis Infections by Peptide Enzyme-Linked Immunosorbent Assays. mSphere. 2018;3(4).","DOI":"10.1128\/mSphere.00253-18"},{"key":"2024111223301742000_2023.08.02.551709v2.39","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1997.d01-167.x"},{"key":"2024111223301742000_2023.08.02.551709v2.40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901072"},{"key":"2024111223301742000_2023.08.02.551709v2.41","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.844-850.2002"},{"key":"2024111223301742000_2023.08.02.551709v2.42","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.58"},{"key":"2024111223301742000_2023.08.02.551709v2.43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01726"},{"key":"2024111223301742000_2023.08.02.551709v2.44","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.1.303-309.2000"},{"key":"2024111223301742000_2023.08.02.551709v2.45","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-009-1225-7"},{"key":"2024111223301742000_2023.08.02.551709v2.46","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.7.4171-4179.2005"},{"key":"2024111223301742000_2023.08.02.551709v2.47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08100.x"},{"key":"2024111223301742000_2023.08.02.551709v2.48","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301657"},{"key":"2024111223301742000_2023.08.02.551709v2.49","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.5.734"},{"key":"2024111223301742000_2023.08.02.551709v2.50","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz087"},{"key":"2024111223301742000_2023.08.02.551709v2.51","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.12.7948"},{"key":"2024111223301742000_2023.08.02.551709v2.52","doi-asserted-by":"crossref","unstructured":"Ogongo P , Tezera LB , Ardain A , Nhamoyebonde S , Ramsuran D , Singh A , et al. Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung. J Clin Invest. 2021;131(10).","DOI":"10.1172\/JCI142014"},{"key":"2024111223301742000_2023.08.02.551709v2.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-021-00407-5"},{"key":"2024111223301742000_2023.08.02.551709v2.54","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e3181ee6a62"},{"key":"2024111223301742000_2023.08.02.551709v2.55","doi-asserted-by":"crossref","unstructured":"Ogendi BMO , Bakshi RK , Sabbaj S , Brown L , Lee JY , Kapil R , et al. Distinct peripheral vs mucosal T-cell phenotypes in chlamydia-infected women. Am J Reprod Immunol. 2017;78(6).","DOI":"10.1111\/aji.12768"},{"key":"2024111223301742000_2023.08.02.551709v2.56","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2008.00639.x"},{"key":"2024111223301742000_2023.08.02.551709v2.57","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4241"},{"key":"2024111223301742000_2023.08.02.551709v2.58","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200874"},{"key":"2024111223301742000_2023.08.02.551709v2.59","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01897-8"},{"key":"2024111223301742000_2023.08.02.551709v2.60","doi-asserted-by":"crossref","unstructured":"Li Y , Warren JA , Poston TB , Clutton G , Shaw FR , Conrad SZ , et al. Chlamydia trachomatis induces low-frequency, sustained CD4 T cell responses in most women, predominantly targeting chlamydial protease-like activity factor, CPAF. J Infect Dis. 2024.","DOI":"10.1093\/infdis\/jiae443"},{"key":"2024111223301742000_2023.08.02.551709v2.61","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00209-09"},{"key":"2024111223301742000_2023.08.02.551709v2.62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228381"},{"key":"2024111223301742000_2023.08.02.551709v2.63","doi-asserted-by":"crossref","unstructured":"Nguyen N , Guleed S , Olsen AW , Follmann F , Christensen JP , and Dietrich J . Th1\/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis. Front Immunol. 2021;12:790463.","DOI":"10.3389\/fimmu.2021.790463"},{"key":"2024111223301742000_2023.08.02.551709v2.64","doi-asserted-by":"crossref","unstructured":"Poston TB , Girardi J , Kim M , Zwarycz P , Polson AG , Yount K , et al. Intranasal immunization with CPAF combined with cyclic-di-AMP induces a memory CD4 T cell response and reduces bacterial burden following intravaginal infection with Chlamydia muridarum. bioRxiv. 2024.","DOI":"10.2139\/ssrn.4962974"},{"key":"2024111223301742000_2023.08.02.551709v2.65","doi-asserted-by":"crossref","unstructured":"Poston TB , Girardi J , Polson AG , Bhardwaj A , Yount KS , Jaras Salas I , et al. Viral- vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non- protective CD8-dominant response in na\u00efve mice. Mucosal Immunol. 2024.","DOI":"10.1016\/j.mucimm.2024.06.012"},{"key":"2024111223301742000_2023.08.02.551709v2.66","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21858"},{"key":"2024111223301742000_2023.08.02.551709v2.67","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037"},{"key":"2024111223301742000_2023.08.02.551709v2.68","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17569-8"},{"key":"2024111223301742000_2023.08.02.551709v2.69","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408792111"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.08.02.551709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:01:37Z","timestamp":1768453297000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.08.02.551709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,3]]},"references-count":69,"URL":"https:\/\/doi.org\/10.1101\/2023.08.02.551709","relation":{},"subject":[],"published":{"date-parts":[[2023,8,3]]},"subtype":"preprint"}}