Lack of LFA1 mediated signals promotes generation of memory precursor effector CD8 T cells during LCMV infection (83.19)

Abstract

Abstract Multiphoton intravital microscopy (MP-IVM) studies have revealed that T cell priming encompasses a prolonged phase of stable interactions between T cell and Dendritic cells (DCs). Although believed to promote T cell activation, the role of prolonged T-DC interactions remains poorly understood. Here we dissect the contribution of LFA1 mediated adhesion/signaling in two settings: in mediating P14 T cell interactions with GP33-39 peptide pulsed DCs and modulating the differentiation of P14 T cells after an LCMV infection. First, we show that the lack of LFA1 on P14 T cells significantly decreases the T-DC interaction time measured by MP-IVM. Second adoptive transfer of physiological numbers of P14 LFA1 -/- T cells into WT recipients generated reduced effector cell numbers at day 8 after LCMV i.p. infection, when compared to P14 LFA1+/+ T cells. Moreover, P14 LFA1-/- T cells were poor cytokine producers and showed a significant increase in the frequency of IL7Rhigh KLRG1low memory precursor effector cells. In summary, our results suggest that prolonged T-DC interactions mediated by LFA1 promote generation of short lived effector cells. In contrast, short lived T-DC interactions promote the generation of memory precursor effector cells.