{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:52:44Z","timestamp":1788562364234,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Overwhelming activation of T cells in acute malaria is associated with severe outcomes. Thus, counter\u2010regulation by anti\u2010inflammatory mechanisms is indispensable for an optimal resolution of disease. Using\n                    <jats:italic>Plasmodium berghei<\/jats:italic>\n                    ANKA (PbA) infection of C57BL\/6 mice, we performed a comprehensive analysis of co\u2010inhibitory molecules expressed on CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells using an unbiased cluster analysis approach. We identified similar T cell clusters co\u2010expressing several co\u2010inhibitory molecules like programmed cell death protein 1 (PD\u20101) and lymphocyte activation gene 3 (LAG\u20103) in the CD4\n                    <jats:sup>+<\/jats:sup>\n                    and the CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell compartment. Interestingly, despite expressing co\u2010inhibitory molecules, which are associated with T cell exhaustion in chronic settings, these T cells were more functional compared to activated T cells that were negative for co\u2010inhibitory molecules. However, T cells expressing high levels of PD\u20101 and LAG\u20103 also conferred suppressive capacity and thus resembled type I regulatory T cells. To our knowledge, this is the first description of malaria\u2010induced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells with suppressive capacity. Importantly, we found an induction of T cells with a similar co\u2010inhibitory rich phenotype in\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    \u2010infected patients. In conclusion, we demonstrate that malaria\u2010induced T cells expressing co\u2010inhibitory molecules are not exhausted, but acquire additional suppressive capacity, which might represent an immune regulatory pathway to prevent further activation of T cells during acute malaria.\n                  <\/jats:p>","DOI":"10.1002\/eji.202149424","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T14:59:28Z","timestamp":1636469968000},"page":"312-327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["T cells expressing multiple co\u2010inhibitory molecules in acute malaria are not exhausted but exert a suppressive function in mice"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6906-6110","authenticated-orcid":false,"given":"Johannes","family":"Brandi","sequence":"first","affiliation":[{"name":"Protozoa Immunology Bernhard Nocht Institute for 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