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- W4313360008 abstract "Abstract T cells of high functional avidity sense and respond to low levels of antigen (Ag), and their superior protective efficacy was first described using CD8 T cells cultured in vitro with low levels of Ag resulting in higher avidity and anti-tumor/viral efficacy compared to low avidity T cells cultured with high Ag concentrations. Selectively inducing high avidity by low Ag concentrations has required in vitro expansion so far, as in vivo attempts with low-dose vaccination gave no response. We show for the first time that functionally high avidity CD4, but not CD8, T cells are selectively primed in vivo by low concentrations of Ag in the strong crosspriming liposomal cationic adjuvant formulations (CAF) DDA/TDB or DDA/MMG/pIC from SSI. Increased functional avidity observed after low-dose vaccinations correlated with lower surface expression of PD-1 and higher per cell IFN-gamma production compared to low avidity CD4 T cells. We further show that IL-15, known to increase functional avidity of CTLs, is essential for high avidity of vaccine specific CD4 T cells. Importantly, high avidity CD4 T cells offered superior protection in a murine model of latent infection with Mycobacterium tuberculosis compared to low avidity T cells. Furthermore, adoptive transfers of HIV-IIIB gp140-specific CD4 T cells of high functional avidity resulting from low-dose immunizations in combination with TCR transgenic HIV-IIIB gp120 specific CTLs conferred superior protection against viral (vaccinia-HIV-IIB-gp140) challenge compared to TCR-Tg CTLs alone or in combination with low avidity CD4 T cells induced by high-dose immunization. Thus, inducing high avidity CD4 T cells by low-dose immunization is important in clearing viral and bacterial infections." @default.
- W4313360008 created "2023-01-06" @default.
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- W4313360008 date "2017-05-01" @default.
- W4313360008 modified "2023-09-27" @default.
- W4313360008 title "Low antigen dose in adjuvant-based vaccination selectively induces CD4 T cells with enhanced functional avidity and protective efficacy" @default.
- W4313360008 doi "https://doi.org/10.4049/jimmunol.198.supp.73.9" @default.
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