The role of interleukin-12 for mTOR regulation of memory CTLs

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dc.contributor.advisorXiao, Zhengguoen_US
dc.contributor.authorGarcia, Karlaen_US
dc.contributor.departmentAnimal Sciencesen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2014-10-17T05:34:19Z
dc.date.available2014-10-17T05:34:19Z
dc.date.issued2014en_US
dc.description.abstractA major goal of vaccines is to induce functional immune memory, and efforts to improve the efficacy of vaccines targeting memory CTLs have revealed an important immunoregulatory role of rapamycin, a specific mTOR inhibitor. While inflammatory cytokines are critical for memory CTLs formation, it is unknown if cytokines such as IL-12 mediate rapamycin's regulation during infection. Inhibition of mTOR by rapamycin represses CTL expansion but enhances central memory during vaccinia virus infection in mice. Without IL-12, immunoregulatory effects of rapamycin on CTL expansion and subsequent memory formation are diminished, yet present compared to CTLs not treated with rapamycin. In infected mice, rapamycin directly enhances IL-12 signaling in WT CTLs by upregulating IL-12 receptor-B2 and STAT4 phosphorylation. Furthermore, secondary expansion of rapamycin-regulated memory CTLs in IL-12 receptor knockouts is impaired and resultant secondary memory CTLs are abolished. This indicates that interplay between cytokines and adjuvants should be considered during vaccine design.en_US
dc.identifierhttps://doi.org/10.13016/M2330M
dc.identifier.urihttp://hdl.handle.net/1903/15950
dc.language.isoenen_US
dc.subject.pqcontrolledImmunologyen_US
dc.subject.pqcontrolledAnimal sciencesen_US
dc.subject.pqcontrolledAnimal diseasesen_US
dc.subject.pquncontrolledIL-12en_US
dc.subject.pquncontrolledMemory CTLsen_US
dc.subject.pquncontrolledmTORen_US
dc.subject.pquncontrolledRapamycinen_US
dc.titleThe role of interleukin-12 for mTOR regulation of memory CTLsen_US
dc.typeThesisen_US

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