LFA-1 and CD62L dependent transient surface CCR5 expression in naïve CD8+ T cells enhances T cell immune memory (CCR3P.214)

Abstract

Abstract The initiation of an effective adaptive immune response requires choreographed interaction among rare antigen-bearing dendritic cells (DCs) with antigen-specific CD4+ and CD8+ T cells in the lymph node (LN). This interaction is especially critical for the magnitude of memory T cell generation. We and others have previously demonstrated that CCL3/CCL4 secretion from productive interaction between antigen-specific T cell and antigen-bearing DCs promote local recruitment of naïve CD8+ T cells in the inflamed LNs, implying that naïve CD8+ T cells can express CCR5 in the inflamed LN microenvironment. Here, we examined the kinetics of CCR5 expression on naïve T cells upon entering an inflamed LN. Maximum surface CCR5 expression occurs in 10-30% of newly arrived naive T cells within the first 6 hours via mobilization of pre-existing CCR5 protein found in intracellular vesicles, and this transient up-regulation of surface CCR5 expression in CD8+ T cells was dependent on direct physical contact with LFA and CD62L, as ligation of CD8+ T cells with anti-CD11a and/or anti-CD62L antibodies enhances surface CCR5 expression within 1 hour in the absence of TCR stimulation. More importantly, CCR5+ fraction of naïve CD8+ T cells exhibit enhanced ability to become memory T cells. Our study implicates an important functional role for CCR5 expression by naïve lymphocytes prior to cognate antigen recognition for enhanced memory T cell development.