{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:12:40Z","timestamp":1761844360610},"reference-count":45,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2014,5,15]],"date-time":"2014-05-15T00:00:00Z","timestamp":1400112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            T-cell functional avidity is a crucial determinant for efficient pathogen clearance. Although recombinant DNA priming coupled with a vaccinia-vectored vaccine (VACV) boost has been widely used to mount robust CD8\n            <jats:sup>+<\/jats:sup>\n            T-cell responses, how VACV boost shapes the properties of memory CD8\n            <jats:sup>+<\/jats:sup>\n            T cells remains poorly defined. Here, we characterize the memory CD8\n            <jats:sup>+<\/jats:sup>\n            T cells boosted by VACV and demonstrate that the intrinsic expression of MyD88 is critical for their high functional avidity. Independent of selection of clones with high-affinity T-cell receptor (TCR) or of enhanced proximal TCR signaling, the VACV boost significantly increased T-cell functional avidity through a decrease in the activation threshold. VACV-induced inflammatory milieu is not sufficient for this improvement, as simultaneous administration of the DNA vaccine and mock VACV had no effects on the functional avidity of memory CD8\n            <jats:sup>+<\/jats:sup>\n            T cells. Furthermore, reciprocal adoptive transfer models revealed that the intrinsic MyD88 pathway is required for instructing the functional avidity of CD8\n            <jats:sup>+<\/jats:sup>\n            T cells boosted by VACV. Taking these results together, the intrinsic MyD88 pathway is required for the high functional avidity of VACV-boosted CD8\n            <jats:sup>+<\/jats:sup>\n            T cells independent of TCR selection or the VACV infection-induced MyD88-mediated inflammatory milieu.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Functional avidity is one of the crucial determinants of T-cell functionality. Interestingly, although it has been demonstrated that a DNA prime-VACV boost regimen elicits high levels of T-cell functional avidity, how VACV changes the low avidity of CD8\n            <jats:sup>+<\/jats:sup>\n            T cells primed by DNA into higher ones\n            <jats:italic>in vivo<\/jats:italic>\n            is less defined. Here, we proved that the enhancement of CD8\n            <jats:sup>+<\/jats:sup>\n            T cell avidity induced by VACV boost is mediated by the intrinsic MyD88 pathway but not the MyD88-mediated inflammatory milieu, which might provide prompts in vaccine design.\n          <\/jats:p>","DOI":"10.1128\/jvi.03664-13","type":"journal-article","created":{"date-parts":[[2014,2,20]],"date-time":"2014-02-20T05:29:07Z","timestamp":1392874147000},"page":"5356-5368","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Boosting Functional Avidity of CD8\n            <sup>+<\/sup>\n            T Cells by Vaccinia Virus Vaccination Depends on Intrinsic T-Cell MyD88 Expression but Not the Inflammatory Milieu"],"prefix":"10.1128","volume":"88","author":[{"given":"Zhidong","family":"Hu","sequence":"first","affiliation":[{"name":"Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key 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