{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:01:18Z","timestamp":1791216078676,"version":"4.1.0"},"reference-count":42,"publisher":"Microbiology Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,6,1]]},"abstract":"<jats:p>The ability of virus-specific CD8<jats:sup>+<\/jats:sup>T cells to produce cytokines was studied in mice infected with lymphocytic choriomeningitis virus and vesicular stomatitis virus. Intracellular staining was used to visualize cytokine-producing CD8<jats:sup>+<\/jats:sup>and CD4<jats:sup>+<\/jats:sup>T cells. Overall, virus-specific CD8<jats:sup>+<\/jats:sup>T cells produce a similar range of cytokines (IFN-<jats:italic>\u03b3<\/jats:italic>, TNF-<jats:italic>\u03b1<\/jats:italic>, IL-2, GM-CSF, RANTES, MIP-1<jats:italic>\u03b1<\/jats:italic>and MIP-1<jats:italic>\u03b2<\/jats:italic>) as CD4<jats:sup>+<\/jats:sup>T cells, but the relative distribution of cytokine-producing subsets is different. Moreover, cytokine-producing CD8<jats:sup>+<\/jats:sup>T cells were found to dominate numerically at all time-points tested. Co-staining for more than one cytokine revealed that while all cytokine-producing CD8<jats:sup>+<\/jats:sup>T cells synthesized IFN-<jats:italic>\u03b3<\/jats:italic>, additional cytokines were produced by partly overlapping subsets of this population. The frequency of cells producing more than one cytokine was higher in a tertiary site (peritoneum) and generally increased with transition into the memory phase; however, GM-CSF producing cells were only present transiently. Concerning factors predicted to influence the distribution of cytokine-producing subsets, IFN-<jats:italic>\u03b3<\/jats:italic>and IL-12 did not play a role, nor was extensive virus replication essential. Notably, regarding the heterogeneity in cytokine production by individual cells with similar epitope specificity, variation in TCR avidity was not the cause, since<jats:italic>in vivo<\/jats:italic>-activated TCR transgene-expressing cells were as heterogeneous in cytokine expression as polyclonal cells specific for the same epitope.<\/jats:p>","DOI":"10.1099\/vir.0.79903-0","type":"journal-article","created":{"date-parts":[[2004,5,27]],"date-time":"2004-05-27T20:48:15Z","timestamp":1085690895000},"page":"1703-1712","source":"Crossref","is-referenced-by-count":21,"title":["Cytokine production by virus-specific CD8+ T cells varies with activation state and localization, but not with TCR avidity"],"prefix":"10.1099","volume":"85","author":[{"given":"Nanna Ny","family":"Kristensen","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas Nygaard","family":"Madsen","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan Randrup","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Pravsgaard","family":"Christensen","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1093\/intimm\/11.12.2035","article-title":"CD4+ T cell-mediated protection against a lethal outcome of systemic infection with vesicular stomatitis virus requires CD40 ligand expression, but not IFN-gamma or IL-4","volume":"11","author":"Andersen","year":"1999","journal-title":"Int Immunol"},{"key":"R2","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.4049\/jimmunol.164.7.3689","article-title":"Role of CD40 ligand and CD28 in induction and maintenance of antiviral CD8+ effector T cell responses","volume":"164","author":"Andreasen","year":"2000","journal-title":"J Immunol"},{"key":"R3","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.4049\/jimmunol.146.12.4301","article-title":"Antiviral protection by CD8+ versus CD4+ T cells. 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