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Robust T cell\u2010based tests are needed to differentiate specific cellular immune responses after infection from those after vaccination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One hundred seventeen individuals (COVID\u201019 convalescent patients: <jats:italic>n<\/jats:italic>\u00a0=\u200940; SARS\u2010CoV\u20102 vaccinees: <jats:italic>n<\/jats:italic>\u00a0=\u200941; healthy controls: <jats:italic>n<\/jats:italic>\u00a0=\u200936) were evaluated for SARS\u2010CoV\u20102\u2010specific cellular immune responses (proliferation, Th1, Th2, Th17, and inflammatory cytokines, activation\u2010induced marker [AIM] expression) by incubating purified peripheral blood mononuclear cells (PBMC) or whole blood (WB) with SARS\u2010CoV\u20102 peptides (S, N, or M), vaccine antigens (tetanus toxoid, tick borne encephalitis virus) or polyclonal stimuli (<jats:italic>Staphylococcal<\/jats:italic> enterotoxin, phytohemagglutinin).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>N\u2010peptide mix stimulation of WB identified the combination of IL\u20102 and IL\u201013 secretion as superior to IFN\u2010\u03b3 secretion to discriminate between COVID\u201019\u2010convalescent patients and healthy controls (<jats:italic>p<\/jats:italic>\u00a0&lt;\u2009.0001). Comparable results were obtained with M\u2010 or S\u2010peptides, the latter almost comparably recalled IL\u20102, IFN\u2010\u03b3, and IL\u201013 responses in WB of vaccinees. Analysis 10\u00a0months as opposed to 10\u2009weeks after COVID\u201019, but not allergic disease status, positively correlated with IL\u201013 recall responses. WB cytokine responses correlated with cytokine and proliferation responses of PBMC. Antigen\u2010induced neo\u2010expression of the C\u2010type lectin CD69 on CD4<jats:sup>+<\/jats:sup> (<jats:italic>p<\/jats:italic>\u00a0&lt;\u2009.0001) and CD8<jats:sup>+<\/jats:sup> (<jats:italic>p<\/jats:italic>\u00a0=\u2009.0002) T cells informed best about the SARS\u2010CoV\u20102 exposure status with additional benefit coming from CD25 upregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Along with N\u2010 and S\u2010peptide\u2010induced IL\u20102 and CD69 neo\u2010expression, we suggest to include the type 2 cytokine IL\u201013 as T\u2010cellular recall marker for SARS\u2010CoV\u20102 specific T\u2010cellular immune responses after infection and vaccination.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15406","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T16:44:25Z","timestamp":1655052265000},"page":"3408-3425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Combined assessment of S\u2010 and N\u2010specific <scp>IL<\/scp>\u20102 and <scp>IL<\/scp>\u201013 secretion and <scp>CD69<\/scp> neo\u2010expression for discrimination of post\u2013infection and post\u2010vaccination cellular <scp>SARS\u2010CoV<\/scp>\u20102\u2010specific immune response"],"prefix":"10.1111","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1091-4327","authenticated-orcid":false,"given":"Bernhard","family":"Kratzer","sequence":"first","affiliation":[{"name":"Medical University of Vienna Center for Pathophysiology Infectiology and Immunology Institute of Immunology  Vienna 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