Browsing by Author "Robins, Elizabeth"
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Item Open Access Definition of a murine CD8+ MHCII-recognizing effector T cell population(2019) Robins, ElizabethCD4+ and CD8+ T cells are dichotomous lineages in adaptive immunity. While conventionally viewed as distinct fates that are fixed post-thymic development, accumulating evidence indicates that these two populations can exhibit significant lineage plasticity, particularly upon TCR-mediated activation. In this work, I define a novel murine CD4-CD8ab+ MHCII-recognizing population generated from effector CD4+ T cells. Effector CD4-CD8ab+ MHCII-recognizing T cells downregulate expression of T helper cell-associated costimulatory molecules and increase expression of cytotoxic T lymphocyte-associated cytotoxic molecules. TCRb repertoire sequencing and in vivo genetic lineage tracing in acutely-infected wild-type mice demonstrate fundamental lineage reprogramming resulting in an “ex-CD4” T cell phenotype, rather than expansion of an aberrantly-developed CD8+ MHCII-restricted population. Impairing autophagy by functional deletion of the initiating kinase Vps34 or a downstream enzyme Atg7 dramatically enhances the generation of effector CD4-CD8ab+ MHCII-recognizing T cells. These findings suggest that effector CD4+ T cells can exhibit a previously unreported degree of skewing towards the CD8+ T cell lineage, which may point towards a novel direction for vaccine design, particularly against HIV.
Item Open Access HLA class II-Restricted CD8+ T cells in HIV-1 Virus Controllers.(Scientific reports, 2019-07-15) Nyanhete, Tinashe E; Frisbee, Alyse L; Bradley, Todd; Faison, William J; Robins, Elizabeth; Payne, Tamika; Freel, Stephanie A; Sawant, Sheetal; Weinhold, Kent J; Wiehe, Kevin; Haynes, Barton F; Ferrari, Guido; Li, Qi-Jing; Moody, M Anthony; Tomaras, Georgia DA paradigm shifting study demonstrated that induction of MHC class E and II-restricted CD8+ T cells was associated with the clearance of SIV infection in rhesus macaques. Another recent study highlighted the presence of HIV-1-specific class II-restricted CD8+ T cells in HIV-1 patients who naturally control infection (virus controllers; VCs). However, questions regarding class II-restricted CD8+ T cells ontogeny, distribution across different HIV-1 disease states and their role in viral control remain unclear. In this study, we investigated the distribution and anti-viral properties of HLA-DRB1*0701 and DQB1*0501 class II-restricted CD8+ T cells in different HIV-1 patient cohorts; and whether class II-restricted CD8+ T cells represent a unique T cell subset. We show that memory class II-restricted CD8+ T cell responses were more often detectable in VCs than in chronically infected patients, but not in healthy seronegative donors. We also demonstrate that VC CD8+ T cells inhibit virus replication in both a class I- and class II-dependent manner, and that in two VC patients the class II-restricted CD8+ T cells with an anti-viral gene signature expressed both CD4+ and CD8+ T cell lineage-specific genes. These data demonstrated that anti-viral memory class II-restricted CD8+ T cells with hybrid CD4+ and CD8+ features are present during natural HIV-1 infection.