{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:49:39Z","timestamp":1789620579039,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["211356\/Z\/18\/Z"],"award-info":[{"award-number":["211356\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cellular immunity against rotavirus in children is incompletely understood. This review describes the current understanding of T-cell immunity to rotavirus in children. A systematic literature search was conducted in Embase, MEDLINE, Web of Science, and Global Health databases using a combination of \u201ct-cell\u201d, \u201crotavirus\u201d and \u201cchild\u201d keywords to extract data from relevant articles published from January 1973 to March 2020. Only seventeen articles were identified. Rotavirus-specific T-cell immunity in children develops and broadens reactivity with increasing age. Whilst occurring in close association with antibody responses, T-cell responses are more transient but can occur in absence of detectable antibody responses. Rotavirus-induced T-cell immunity is largely of the gut homing phenotype and predominantly involves Th1 and cytotoxic subsets that may be influenced by IL-10 Tregs. However, rotavirus-specific T-cell responses in children are generally of low frequencies in peripheral blood and are limited in comparison to other infecting pathogens and in adults. The available research reviewed here characterizes the T-cell immune response in children. There is a need for further research investigating the protective associations of rotavirus-specific T-cell responses against infection or vaccination and the standardization of rotavirus-specific T-cells assays in children.<\/jats:p>","DOI":"10.3390\/v14030459","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:53:26Z","timestamp":1645664006000},"page":"459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["T-Cell Responses after Rotavirus Infection or Vaccination in Children: A Systematic Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6217-0289","authenticated-orcid":false,"given":"Natasha Makabilo","family":"Laban","sequence":"first","affiliation":[{"name":"Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK"},{"name":"Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8963-4768","authenticated-orcid":false,"given":"Martin Rhys","family":"Goodier","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK"},{"name":"Flow Cytometry and Immunology Facility, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul P.O. Box 273, The Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Bosomprah","sequence":"additional","affiliation":[{"name":"Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia"},{"name":"Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelo","family":"Simuyandi","sequence":"additional","affiliation":[{"name":"Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Chisenga","sequence":"additional","affiliation":[{"name":"Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3593-1895","authenticated-orcid":false,"given":"Obvious Nchimunya","family":"Chilyabanyama","sequence":"additional","affiliation":[{"name":"Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roma","family":"Chilengi","sequence":"additional","affiliation":[{"name":"Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): A prospective, case-control study","volume":"382","author":"Kotloff","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e568","DOI":"10.1016\/S2214-109X(19)30076-2","article-title":"The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: A 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS)","volume":"7","author":"Kotloff","year":"2019","journal-title":"Lancet Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S1473-3099(18)30362-1","article-title":"Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Troeger","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1093\/infdis\/jix186","article-title":"Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality From Diarrhea","volume":"215","author":"Burnett","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1093\/cid\/civ1015","article-title":"Health Impact of Rotavirus Vaccination in Developing Countries: Progress and Way Forward","volume":"62","author":"Parashar","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/QCO.0000000000000572","article-title":"Current and new rotavirus vaccines","volume":"32","author":"Burke","year":"2019","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.4161\/hv.34361","article-title":"Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges","volume":"10","author":"Angel","year":"2014","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.virusres.2014.06.016","article-title":"Rotaviruses","volume":"190","author":"Desselberger","year":"2014","journal-title":"Virus Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1056\/NEJM199610033351404","article-title":"Rotavirus Infection in Infants as Protection against Subsequent Infections","volume":"335","author":"Matson","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/infdis\/jiq031","article-title":"Immune responses to rotavirus infection and vaccination and associated correlates of protection","volume":"203","author":"Desselberger","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chilengi, R., Simuyandi, M., Beach, L., Mwila, K., Becker-Dreps, S., Emperador, D.M., Velasquez, D.E., Bosomprah, S., and Jiang, B. (2016). Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150100"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/infdis\/jiaa068","article-title":"Postvaccination Serum Antirotavirus Immunoglobulin A as a Correlate of Protection Against Rotavirus Gastroenteritis Across Settings","volume":"222","author":"Baker","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/cid\/ciy076","article-title":"Rotavirus-Specific Immunoglobulin A Responses Are Impaired and Serve as a Suboptimal Correlate of Protection Among Infants in Bangladesh","volume":"67","author":"Lee","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8735","DOI":"10.1128\/jvi.71.11.8735-8742.1997","article-title":"Evidence that resolution of rotavirus infection in mice is due to both CD4 and CD8 cell-dependent activities","volume":"71","author":"McNeal","year":"1997","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1128\/JVI.76.2.560-568.2002","article-title":"CD4 T cells are the only lymphocytes needed to protect mice against rotavirus shedding after intranasal immunization with a chimeric VP6 protein and the adjuvant LT(R192G)","volume":"76","author":"McNeal","year":"2002","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1128\/JVI.72.1.726-730.1998","article-title":"Expression of the mucosal homing receptor \u03b14\u03b27 correlates with the ability of CD8+ memory T cells to clear rotavirus infection","volume":"72","author":"Williams","year":"1998","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1080\/21645515.2020.1844525","article-title":"Update on rotavirus vaccine underperformance in low- to middle-income countries and next-generation vaccines","volume":"17","author":"Lee","year":"2021","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., and The, P.G. (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shrotri, M., van Schalkwyk, M.C.I., Post, N., Eddy, D., Huntley, C., Leeman, D., Rigby, S., Williams, S.V., Bermingham, W.H., and Kellam, P. (2021). T cell response to SARS-CoV-2 infection in humans: A systematic review. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0245532"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1002\/jmv.26891","article-title":"Toward an understanding of regulatory T cells in COVID-19: A systematic review","volume":"93","author":"Rahimzadeh","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"679","DOI":"10.3892\/etm.2015.2511","article-title":"Changes in the cytokine expression of peripheral Treg and Th17 cells in children with rotavirus enteritis","volume":"10","author":"Dong","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/02724936.1992.11747550","article-title":"A Study on Delayed-Hypersensitivity to Rotavirus in Infancy and Childhood","volume":"12","author":"Elaraby","year":"1992","journal-title":"Ann. Trop. Paediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.3748\/wjg.14.1630","article-title":"Protein-loosing enteropathy associated with rotavirus infection in an infant","volume":"14","author":"Iwasa","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1128\/JVI.76.10.4741-4749.2002","article-title":"Frequencies of virus-specific CD4+ and CD8+ T lymphocytes secreting gamma interferon after acute natural rotavirus infection in children and adults","volume":"76","author":"Jaimes","year":"2002","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1365-2249.2006.03146.x","article-title":"Rotavirus-specific T cell responses and cytokine mRNA expression in children with diabetes-associated autoantibodies and type 1 diabetes","volume":"145","author":"Makela","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1365-2249.2004.02509.x","article-title":"Rotavirus-specific T-cell responses in young prospectively followed-up children","volume":"137","author":"Makela","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.virol.2009.12.016","article-title":"A TGF-beta mediated regulatory mechanism modulates the T cell immune response to rotavirus in adults but not in children","volume":"399","author":"Mesa","year":"2010","journal-title":"Virology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/infdis\/165.6.1107","article-title":"Rotavirus-specific helper T cell responses in newborns, infants, children, and adults","volume":"165","author":"Offit","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1093\/infdis\/167.6.1436","article-title":"Rotavirus-specific humoral and cellular immune response after primary, symptomatic infection","volume":"167","author":"Offit","year":"1993","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.virol.2014.08.020","article-title":"Circulating rotavirus-specific T cells have a poor functional profile","volume":"468","author":"Parra","year":"2014","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.virol.2014.01.014","article-title":"Circulating human rotavirus specific CD4 T cells identified with a class II tetramer express the intestinal homing receptors \u03b14\u03b27 and CCR9","volume":"452","author":"Parra","year":"2014","journal-title":"Virology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0042-6822(03)00507-5","article-title":"Human rotavirus specific T cells: Quantification by ELISPOT and expression of homing receptors on CD4+ T cells","volume":"314","author":"Rojas","year":"2003","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1172\/JCI119633","article-title":"Expression of mucosal homing receptor alpha4beta7 by circulating CD4+ cells with memory for intestinal rotavirus","volume":"100","author":"Rott","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1128\/JVI.01887-06","article-title":"Rotavirus Infection Alters Peripheral T-Cell Homeostasis in Children with Acute Diarrhea","volume":"81","author":"Wang","year":"2007","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.3389\/fimmu.2017.02002","article-title":"B and T cell phenotypic profiles of African HIV-infected and HIV-exposed uninfected infants: Associations with antibody responses to the pentavalent rotavirus vaccine","volume":"8","author":"Weinberg","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/jmv.1890240410","article-title":"Chronic enteric virus infection in two T-cell immunodeficient children","volume":"24","author":"Wood","year":"1988","journal-title":"J. Med. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1365-2249.1990.tb06440.x","article-title":"Rotavirus induces proliferative response and augments non-specific cytotoxic activity of lymphocytes in humans","volume":"80","author":"Yasukawa","year":"1990","journal-title":"Clin. Exp. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7328","DOI":"10.1016\/j.vaccine.2017.03.076","article-title":"The rotavirus vaccine development pipeline","volume":"37","author":"Kirkwood","year":"2019","journal-title":"Vaccine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1056\/NEJMoa1706804","article-title":"Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth","volume":"378","author":"Bines","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Cunliffe, N., Zaman, K., Rodrigo, C., Debrus, S., Benninghoff, B., Pemmaraju Venkata, S., and Han, H.-H. (2014). Early exposure of infants to natural rotavirus infection: A review of studies with human rotavirus vaccine RIX4414. BMC Pediatr., 14.","DOI":"10.1186\/s12887-014-0295-2"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S146","DOI":"10.1086\/431499","article-title":"Serotype Diversity and Reassortment between Human and Animal Rotavirus Strains: Implications for Rotavirus Vaccine Programs","volume":"192","author":"Gentsch","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Steele, A.D., Neuzil, K.M., Cunliffe, N.A., Madhi, S.A., Bos, P., Ngwira, B., Witte, D., Todd, S., Louw, C., and Kirsten, M. (2012). Human rotavirus vaccine Rotarix\u2122 provides protection against diverse circulating rotavirus strains in African infants: A randomized controlled trial. BMC Infect. Dis., 12.","DOI":"10.1186\/1471-2334-12-213"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.virusres.2016.03.006","article-title":"Evaluation of oral Lanzhou lamb rotavirus vaccine via passive transfusion with CD4+\/CD8+ T lymphocytes","volume":"217","author":"Du","year":"2016","journal-title":"Virus Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1128\/JVI.01877-06","article-title":"Association of gamma interferon and interleukin-17 production in intestinal CD4+ T cells with protection against rotavirus shedding in mice intranasally immunized with VP6 and the adjuvant LT(R192G)","volume":"81","author":"Smiley","year":"2007","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1053\/j.gastro.2018.06.078","article-title":"Expression of CCR6 and CXCR6 by Gut-Derived CD4+\/CD8\u03b1+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases","volume":"155","author":"Godefroy","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1097\/QCO.0000000000000189","article-title":"Innate-like lymphocytes in intestinal infections","volume":"28","author":"Bennett","year":"2015","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hildreth, A.D., and O\u2019sullivan, T.E. (2019). Tissue-resident innate and innate-like lymphocyte responses to viral infection. Viruses, 11.","DOI":"10.3390\/v11030272"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41598-017-18973-9","article-title":"Inactivated rotavirus vaccine by parenteral administration induces mucosal immunity in mice","volume":"8","author":"Resch","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S1473-3099(17)30242-6","article-title":"Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: A randomised, double-blind, placebo-controlled trial","volume":"17","author":"Groome","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.1016\/j.vaccine.2014.05.008","article-title":"Challenges in vaccination of neonates, infants and young children","volume":"32","author":"Pichichero","year":"2014","journal-title":"Vaccine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.3389\/fimmu.2020.01083","article-title":"Limited Impact of Human Cytomegalovirus Infection in African Infants on Vaccine-Specific Responses Following Diphtheria-Tetanus-Pertussis and Measles Vaccination","volume":"11","author":"Cox","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5766","DOI":"10.1128\/JVI.00052-07","article-title":"Cytomegalovirus infection in Gambian infants leads to profound CD8 T-cell differentiation","volume":"81","author":"Miles","year":"2007","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/3\/459\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:26:36Z","timestamp":1760135196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/3\/459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["v14030459"],"URL":"https:\/\/doi.org\/10.3390\/v14030459","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,23]]}}}