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cd4^＋ T-cell dependence of primary cd8^＋ T-cell response against vaccinia virus depends upon route of infection and viral dose

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Cellular & Molecular Immunology 2016年第1期13卷 82-93页

作者： Zhuting Hu Michael J Molloy Edward J Usherwood _Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth Lebanon NH USA

cd4^＋ T-cell help （cd4 help） plays a pivotal role in cd8^＋ T-cell responses against viral infections. However, the role in primary cd8^＋ T-cell responses remains controversial. We evaluated the effects of infection route and viral dose on primary cd8^＋ T-cell responses to vaccinia virus （VACV） in MHC class II^-/- mice. cd4 help deficiency diminished the generation of VACV-specific cd8^＋ T cells after intraperitoneal （i.p.） but not after intranasal （i.n.） infection. A large viral dose could not restore normal expansion of VACV-specific cd8^＋ T cells in i.p. infected MHC II-/- mice. In contrast, dependence on cd4 help was observed in i.n. infected MHC II-/- mice when a small viral dose was used. These data suggested that primary cd8~ T-cell responses are less dependent on cd4 help in i.n. infection compared to i.p. infection. Activated cd8~ T cells produced more I FN-y, TNF-a and granzyme B in i.n. infected mice than those in i.p. infected mice, regardless of cd4 help. IL-2 signaling via cd25 was not necessary to drive expansion of VACV-specific cd8~ T cells in i.n. infection, but it was crucial in i.p. infection. VACV-specific cd8^＋ T cells underwent increased apoptosis in the absence of cd4 help, but proliferated normally and had cytotoxic potential, regardless of infection route. Our results indicate that route of infection and viral dose are two determinants for cd4 help dependence, and intranasal infection induces more potent effector cd8^＋ T cells than i.D. infection.

关键词： cd4 help MHC II^-/- mice primary cd8^+ T-cell response vaccinia virus

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Dendritic cells in cancer immunology

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Cellular & Molecular Immunology 2022年第1期19卷 3-13页

作者： Theresa L.Murphy Kenneth M.Murphy Department of Pathology and Immunology Washington University in St.LouisSchool of MedicineSt.LouisMO 63110USA

The clinical success of immune checkpoint therapy(ICT)has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune *** of the current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted *** these principles through continuous basic research may help broaden translational *** this mindset,we focused this review on three threads of basic research directly relating to mechanisms underlying ***,this review covers three aspects of dendritic cell(DC)biology connected with antitumor immune responses but are not specifically oriented toward therapeutic ***,we review recent advances in the development of the cdC1 subset of DCs,identifying important features distinguishing these cells from other types of ***,we review the antigen-processing pathway called cross-presentation,which was discovered in the mid-1970s and remains an *** pathway serves an essential in vivo function unique to cdC1s and may be both a physiologic bottleneck and therapeutic ***,we review the longstanding field of helper cells and the related area of DC licensing,in which cd4 T cells influence the strength or quality of cd8 T cell *** topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.

关键词： Dendritic cells transcription factors cross-presentation tumor rejection cd4 help

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