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]