{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:52:57Z","timestamp":1791190377855,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Assignment","award":["122030900051-9"],"award-info":[{"award-number":["122030900051-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Bordetella pertussis elicits both innate and adaptive cellular responses, yet their relative contributions to peripheral interferon-\u03b3 (IFN-\u03b3) measurements and the temporal dynamics of circulating T-cell reactivity in adults remain incompletely defined. B. pertussis-reactive cellular immunity was investigated in 42 adult donors, including 26 healthy donors and 16 donors with a history of pertussis, using standard and modified IFN-\u03b3 enzyme-linked immunospot (ELISpot) assays with a chemically inactivated whole-cell B. pertussis preparation, bacterial innate-biased stimuli, and a peptide-based T-cell recall control, together with human leukocyte antigen A*02 (HLA-A*02) genotyping. Short-term stimulation of unfractionated peripheral blood mononuclear cells (PBMCs) generated readily detectable IFN-\u03b3 spot formation that was not clearly stratified by childhood vaccination background or previous pertussis history. In a subset of seven donors, lipopolysaccharide and B. pertussis-derived lipooligosaccharide generated strong total PBMC signals but little detectable pattern-defined T-cell-associated spot formation, whereas the whole-cell pertussis preparation retained a detectable T-cell-associated component under modified assay conditions. Among seven donors available for longitudinal follow-up after pertussis, pattern-defined T-cell-associated IFN-\u03b3 spot frequencies in peripheral blood were highest at the recovery sampling point, were significantly reduced at one month, decreased further by three months, remained markedly reduced at six months, and approached background levels at 12 months after recovery. Directly measured CD8+ IFN-\u03b3 responses were preferentially detected in HLA-A*02-positive donors. These findings indicate that cellular composition and sampling time affect the interpretation of peripheral IFN-\u03b3 responses to B. pertussis and show an association between HLA-A*02 status and detectable CD8+ reactivity.<\/jats:p>","DOI":"10.3390\/cells15191807","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:00:22Z","timestamp":1791187222000},"page":"1807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dissecting Adult Peripheral Cellular Immunity to Bordetella pertussis: Innate-Associated IFN-\u03b3 Responses, Transient T-Cell Recall, and HLA-A*02-Associated CD8+ Reactivity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7058-9223","authenticated-orcid":false,"given":"Alexandra","family":"Maleeva","sequence":"first","affiliation":[{"name":"Research Institute for Systems Biology and Medicine (RISBM), Scientific Driveway, 18, Moscow 117246, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-9052","authenticated-orcid":false,"given":"Varvara","family":"Shokina","sequence":"additional","affiliation":[{"name":"Research Institute for Systems Biology and Medicine (RISBM), Scientific Driveway, 18, Moscow 117246, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Zlata","family":"Naydenysheva","sequence":"additional","affiliation":[{"name":"Research Institute for Systems Biology and Medicine (RISBM), Scientific Driveway, 18, Moscow 117246, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-2076","authenticated-orcid":false,"given":"Anna","family":"Lyapina","sequence":"additional","affiliation":[{"name":"Research Institute for Systems Biology and Medicine (RISBM), Scientific Driveway, 18, Moscow 117246, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6793-6207","authenticated-orcid":false,"given":"Eleonora","family":"Sadykova","sequence":"additional","affiliation":[{"name":"Research Institute for Systems Biology and Medicine (RISBM), Scientific Driveway, 18, Moscow 117246, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1128\/CMR.00083-15","article-title":"Pertussis: Microbiology, Disease, Treatment, and Prevention","volume":"29","author":"Kilgore","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.coi.2019.03.006","article-title":"Pertussis vaccines and protective immunity","volume":"59","author":"Kapil","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.chom.2023.06.015","article-title":"T cell reactivity to Bordetella pertussis is highly diverse regardless of childhood vaccination","volume":"31","author":"Antunes","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1038\/s41467-025-58460-8","article-title":"Th1 polarization in Bordetella pertussis vaccine responses is maintained through a positive feedback loop","volume":"16","author":"Willemsen","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e518","DOI":"10.1093\/infdis\/jiae034","article-title":"IL-17 and IFN-\u03b3\u2013producing Respiratory Tissue-Resident Memory CD4 T Cells Persist for Decades in Adults Immunized as Children with Whole-Cell Pertussis Vaccines","volume":"230","author":"McCarthy","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.vaccine.2013.10.056","article-title":"Different T cell memory in preadolescents after whole-cell or acellular pertussis vaccination","volume":"32","author":"Smits","year":"2013","journal-title":"Vaccine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1172\/JCI121309","article-title":"Th1\/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters","volume":"128","author":"Antunes","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1128\/iai.61.2.399-410.1993","article-title":"Cell-mediated immunity to Bordetella pertussis: Role of Th1 cells in bacterial clearance in a murine respiratory infection model","volume":"61","author":"Mills","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1084\/jem.191.11.1841","article-title":"Protective Immunity to Bordetella pertussis Requires Both B Cells and Cd4+ T Cells for Key Functions Other than Specific Antibody Production","volume":"191","author":"Leef","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tomas, J., Koo, Y., Popoff, D., Arce-Gorvel, V., Hanniffy, S., Gorvel, J.-P., and Mionnet, C. (2021). PTX Instructs the Development of Lung-Resident Memory T Cells in Bordetella pertussis Infected Mice. Toxins, 13.","DOI":"10.3390\/toxins13090632"},{"key":"ref_11","first-page":"e167210","article-title":"Maternal acellular pertussis vaccination in mice impairs cellular immunity to Bordetella pertussis infection in offspring","volume":"8","author":"Dubois","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0165-2478(99)00070-X","article-title":"Interferon-\u03b3 mediated immune effector mechanisms against Bordetella pertussis","volume":"68","author":"Mahon","year":"1999","journal-title":"Immunol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1128\/IAI.01031-09","article-title":"Intracellular Trafficking of Bordetella pertussis in Human Macrophages","volume":"78","author":"Lamberti","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1128\/iai.65.6.2168-2174.1997","article-title":"Vaccine- and antigen-dependent type 1 and type 2 cytokine induction after primary vaccination of infants with whole-cell or acellular pertussis vaccines","volume":"65","author":"Ausiello","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lambert, E.E., Corbi\u00e8re, V., Brink, J.A.M.v.G.-V.D., Duijst, M., Venkatasubramanian, P.B., Simonetti, E., Huynen, M., Diavatopoulos, D.D., Versteegen, P., and Berbers, G.A.M. (2020). Uncovering Distinct Primary Vaccination-Dependent Profiles in Human Bordetella pertussis Specific CD4+ T-Cell Responses Using a Novel Whole Blood Assay. Vaccines, 8.","DOI":"10.3390\/vaccines8020225"},{"key":"ref_16","first-page":"795958","article-title":"Both CD4+ and CD8+ Lymphocytes Participate in the IFN-\u03b3 Response to Filamentous Hemagglutinin from Bordetella pertussis in Infants, Children, and Adults","volume":"2012","author":"Dirix","year":"2012","journal-title":"J. Immunol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.humimm.2014.02.013","article-title":"Substantial gaps in knowledge of Bordetella pertussis antibody and T cell epitopes relevant for natural immunity and vaccine efficacy","volume":"75","author":"Vaughan","year":"2014","journal-title":"Hum. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/978-1-0716-3754-8_17","article-title":"Assessing antigen-specific T cell responses through IFN-\u03b3 enzyme-linked immune absorbent spot (ELISpot)","volume":"2782","author":"Heeren","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kroes, M.M., Mariman, R., Hijdra, D., Hamstra, H.-J., van Boxtel, K.J.W.M., van Putten, J.P.M., de Wit, J., and Pinelli, E. (2019). Activation of Human NK Cells by Bordetella pertussis Requires Inflammasome Activation in Macrophages. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02030"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1093\/infdis\/jiaa140","article-title":"Bordetella pertussis Induces Interferon Gamma Production by Natural Killer Cells, Resulting in Chemoattraction by Respiratory Epithelial Cells","volume":"225","author":"Hartog","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_21","first-page":"453","article-title":"A simplified PCR-SSP method for HLA-A2 subtype in a population of Wuhan, China","volume":"3","author":"Liang","year":"2006","journal-title":"Cell. Mol. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7.1.1","DOI":"10.1002\/0471142735.im0701s85","article-title":"Isolation of Whole Mononuclear Cells from Peripheral Blood and Cord Blood","volume":"85","author":"Fuss","year":"2009","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lambert, E.E., van Twillert, I., Beckers, L., Poelen, M.C.M., Han, W.G.H., Pieren, D.K.J., and van Els, C.A.C.M. (2022). Reduced Bordetella pertussis-specific CD4+ T-Cell Responses at Older Age. Front. 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