{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:29:51Z","timestamp":1767180591917,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pntd.0008969","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000}}],"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["142250\/2016-3"],"award-info":[{"award-number":["142250\/2016-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["310329\/2019-1"],"award-info":[{"award-number":["310329\/2019-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018824","name":"INCT-NIM","doi-asserted-by":"crossref","award":["465489\/2014-1"],"award-info":[{"award-number":["465489\/2014-1"]}],"id":[{"id":"10.13039\/501100018824","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Oswaldo Cruz Institute\/Fiocruz","award":["institutional internal grant"],"award-info":[{"award-number":["institutional internal grant"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    CD8 T cells are regarded as pivotal players in both immunoprotection and immunopathology following\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    infection. Previously, we demonstrated the expansion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes in the spleen of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>cruzi<\/jats:italic>\n                    -infected mice under treatment with benznidazole (N-benzyl-2-nitroimidazole acetamide; Bz), a drug available for clinical therapy. This finding underlies the concept that the beneficial effects of Bz on controlling acute\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>cruzi<\/jats:italic>\n                    infection are related to a synergistic process between intrinsic trypanocidal effect and indirect triggering of the active immune response. In the present study, we particularly investigated the effect of Bz treatment on the CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell subset following\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>cruzi<\/jats:italic>\n                    infection. Herein we demonstrated that, during acute\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>cruzi<\/jats:italic>\n                    infection, Bz treatment reduces and abbreviates the parasitemia, but maintains elevated expansion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Within this subset, a remarkable group of CD8\n                    <jats:sup>low<\/jats:sup>\n                    cells was found in both Bz-treated and non-treated infected mice. In Bz-treated mice, early pathogen control paralleled the lower frequency of recently activated CD8\n                    <jats:sup>low<\/jats:sup>\n                    cells, as ascertained by CD69 expression. However, the CD8\n                    <jats:sup>low<\/jats:sup>\n                    subset sustains significant levels of CD44\n                    <jats:sup>high<\/jats:sup>\n                    CD62L\n                    <jats:sup>low<\/jats:sup>\n                    and CD62L\n                    <jats:sup>low<\/jats:sup>\n                    T-bet\n                    <jats:sup>high<\/jats:sup>\n                    effector memory T cells, in both Bz-treated and non-treated infected mice. These CD8\n                    <jats:sup>low<\/jats:sup>\n                    cells also comprise the main group of spontaneous interferon (IFN)-\u03b3-producing CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Interestingly, following\n                    <jats:italic>in vitro<\/jats:italic>\n                    anti-CD3\/CD28 stimulation, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from Bz-treated\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>cruzi<\/jats:italic>\n                    -infected mice exhibited higher frequency of IFN-\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    cells, which bear mostly a CD8\n                    <jats:sup>low<\/jats:sup>\n                    phenotype. Altogether, our results point to the marked presence of CD8\n                    <jats:sup>low<\/jats:sup>\n                    T cells that arise during acute\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>cruzi<\/jats:italic>\n                    infection, with Bz treatment promoting their significant expansion along with a potential effector program for high IFN-\u03b3 production.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0008969","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T14:25:48Z","timestamp":1608560748000},"page":"e0008969","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["CD8low T cells expanded following acute Trypanosoma cruzi infection and benznidazole treatment are a relevant subset of IFN-\u03b3 producers"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6742-6581","authenticated-orcid":true,"given":"Alessandro","family":"Marins-Dos-Santos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Perdig\u00e3o","family":"Olivieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7417-7867","authenticated-orcid":true,"given":"Rafaella","family":"Ferreira-Reis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"de Meis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-6128","authenticated-orcid":true,"given":"Andrea Alice","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8233-5845","authenticated-orcid":true,"given":"Tania C.","family":"de Ara\u00fajo-Jorge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-6754","authenticated-orcid":true,"given":"Joseli","family":"Lannes-Vieira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6753-3480","authenticated-orcid":true,"given":"Vinicius","family":"Cotta-de-Almeida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,21]]},"reference":[{"key":"pntd.0008969.ref001","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.actatropica.2009.11.003","article-title":"Chagas disease: a Latin American health problem becoming a world health problem","volume":"115","author":"GA Schmunis","year":"2010","journal-title":"Acta Trop"},{"key":"pntd.0008969.ref002","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1590\/0074-0276130565","article-title":"Chagas disease: control, elimination and eradication. 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