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Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19\u2010specific CD4<jats:sup>+<\/jats:sup> CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19\u2010specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19\u2010VP2 virus\u2010like particles. The cytolytic potential was determined by enzyme immunoassay\u2010based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19\u2010seropositive individuals. T\u2010cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4<jats:sup>+<\/jats:sup> T cells. CD4<jats:sup>+<\/jats:sup> T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19\u2010specific CD4<jats:sup>+<\/jats:sup> T cells showed expected co\u2010expression of GrB, perforin and interferon gamma (IFN\u2010\u03b3). Unexpectedly, also a strong co\u2010expression of GrB and interleukin 17 (IL\u201017) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus\u2010specific CD4<jats:sup>+<\/jats:sup> CTLs co\u2010expressing CD56 antigen. Our results suggest a role for CD4<jats:sup>+<\/jats:sup> CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis.<\/jats:p>","DOI":"10.1038\/cti.2015.13","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T07:21:54Z","timestamp":1435908114000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Granzyme B mediated function of Parvovirus B19\u2010specific CD4<sup>+<\/sup> T cells"],"prefix":"10.1002","volume":"4","author":[{"given":"Arun","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Virology, Haartman Institute, University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F","family":"Perdomo","sequence":"additional","affiliation":[{"name":"Department of Virology, Haartman Institute, University of Helsinki  Helsinki 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