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We sought to evaluate the impact of injectable contraceptive use on T\u2010cell responsiveness using T cells exposed in vivo and tested ex vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells were obtained from healthy, HIV\u2010negative women after 30, 90 and 180\u00a0days of DMPA, norethisterone enanthate (Net\u2010En) or copper intrauterine device (Cu\u2010IUD) contraceptive use. Cells were stimulated ex vivo with phorbol myristate acetate and ionomycin, stained and analysed using flow cytometry. Mixed\u2010effects linear models were used to evaluate change in proportions of T cells producing IFN\u2010\u03b3, TNF\u2010\u03b1, IL\u20104 and IL\u201013.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with baseline, decreased proportions of IFN\u2010\u03b3\u2013producing CD4+ and CD8+ T cells (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.003, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.006, respectively) and TNF\u2010\u03b1\u2013producing CD4+ and CD8+ T cells (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.039, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.034, respectively) were observed after 180\u00a0days of DMPA use. Decreased IL\u20104\u2013producing CD4+ and CD8+ T cells (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.045 and <jats:italic>p<\/jats:italic>\u00a0=\u00a0.024, respectively) were noted after 180\u00a0days of Net\u2010En use. Decreased IL\u20104\u2013producing CD4+ T cells were observed after 30\u00a0days (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.035) and not after 180\u00a0days of DMPA use (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.49). There were no changes in proportion of T cells producing IL\u201013 in DMPA users, nor any changes in IFN\u2010\u03b3, TNF\u2010\u03b1 and IL\u201013 in Net\u2010En and Cu\u2010IUD users.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In vivo exposure of CD4+ and CD8+ T cells to typical pharmacologic concentrations of DMPA does not cause broad suppression to stimuli; however, depletion of specific cytokine\u2010producing T cells may occur after prolonged DMPA use.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13405","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T14:31:23Z","timestamp":1613831483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effect of injectable progestin\u2010only contraceptives, depot medroxyprogesterone acetate and norethisterone enanthate, on cytokine production during T\u2010cell activation"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5361-7686","authenticated-orcid":false,"given":"Allen T.","family":"Matubu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Zimbabwe\u2010Clinical Trials Research Centre Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Hillier","sequence":"additional","affiliation":[{"name":"School of Medicine Department of Obstetrics, Gynaecology and Reproductive Sciences University of Pittsburgh Pittsburgh PA USA"},{"name":"Magee\u2010Womens Research Institute Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie A.","family":"Meyn","sequence":"additional","affiliation":[{"name":"School of Medicine Department of Obstetrics, Gynaecology and Reproductive Sciences University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Stoner","sequence":"additional","affiliation":[{"name":"Magee\u2010Womens Research Institute Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Mhlanga","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Zimbabwe\u2010Clinical Trials Research Centre Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Mbizvo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Zimbabwe\u2010Clinical Trials Research Centre Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Maramba","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences Department of Medical Laboratory Sciences University of Zimbabwe Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvavahera M.","family":"Chirenje","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Zimbabwe\u2010Clinical Trials Research Centre Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7478-8262","authenticated-orcid":false,"given":"Sharon L.","family":"Achilles","sequence":"additional","affiliation":[{"name":"School of Medicine Department of Obstetrics, Gynaecology and Reproductive Sciences University of Pittsburgh Pittsburgh PA USA"},{"name":"Magee\u2010Womens Research Institute Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"UNAIDS. 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