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Abstract: LFA-1 signaling is required for the generation of central memory CD8+ T cells in priming phase. However, its role for effector and memory CD8+ T cell survival in transition and maintenance phases is elusive. We transferred effector and memory CD8+ T cells into C57BL/6 and CD54−/− mice, which were generated by cultivation of ovalbumin (OVA)-pulsed dendritic cells (DCOVA) with naïve CD8+ T cells derived from transgenic OT I mice and purified from effector CD8+ T cell-transferred C57BL/6 mice, respectively. We then assessed kinetics of T cell survival using PE-H2-Kb/OVAI tetramer and FITC-CD8 staining by flow cytometry. We found that survival of transferred effector and memory CD8+ T cells in CD54−/− mice significantly decreased (p <0.05) compared to that in C57BL/6 mice due to an increased T cell apoptosis, which is mediated via downregulation of proapoptotic Bid, anti-apoptotic Bcl-2, Bcl-XL and pro-Caspase-8, and up-regulation of apoptotic Bax and cleaved Caspase-3 and -7 by RNA array and Western blotting analyses. Decreased expression of CD27 and IL-15R on transferred CD8+ T cells with less survival was found to be associated with increased T cell apoptosis, which was confirmed by silencing CD27 with siRNA transfection or using CD8+ (IL-15R−/−)T cells for adoptive transfer into C57BL/6 mice. These data indicate that LFA-1 signal defect-induced CD8+ T cell apoptosis is associated with reduced CD27 costimulation and IL-15R survival signal. Therefore, our study provides important evidence on and elucidates the molecular mechanism associated with the role LFA-1 signaling plays in effector and memory CD8+ T cell survival. [ABSTRACT FROM AUTHOR]

• We evaluated the immunogenicity of a rDBPII vaccine with different variables. • Significant variations in immune responses were observed with different variables. • No specific pattern in immune responses with respect to sex or adjuvant observed. • Sex and immune genes are critical variables to consider in vaccine study design. Relapsing malaria caused by Plasmodium vivax is a neglected tropical disease and an important cause of malaria worldwide. Vaccines to prevent clinical disease and mosquito transmission of vivax malaria are needed to overcome the distinct challenges of this important public health problem. In this vaccine immunogenicity study in mice, we examined key variables of responses to a P. vivax Duffy binding protein vaccine, a leading candidate to prevent the disease-causing blood-stages. Significant sex-dependent differences were observed in B cell (CD80+) and T cell (CD8+) central memory subsets, resulting in significant differences in functional immunogenicity and durability of anti-DBP protective efficacy. These significant sex-dependent differences in inbred mice were in the CD73+CD80+ memory B cell, H2KhiCD38hi/lo, and effector memory subsets. This study highlights sex and immune genes as critical variables that can impact host responses to P. vivax antigens and must be taken into consideration when designing clinical vaccine studies. [ABSTRACT FROM AUTHOR]