Trogocytosis-Mediated Signaling Is Associated with Development of a Pre-Germinal Center TFH Phenotype 3046

Abstract Description During trogocytosis, membrane and membrane-associated proteins are transferred directly from APCs to recipient T cells at the immunological synapse. Trogocytosis readily occurs during CD4 T cell activation, however, the biological significance of these APC-derived molecules on the T cell remains unclear. We have previously shown that trogocytosed molecules drive sustained intracellular TCR signaling (elevated phospho-ZAP-70, phospho-Erk 1/2 and total phospho-tyrosine) after removal of APC, leading to preferential survival in culture. This signaling is associated with upregulated GATA-3 expression and the differentiation of cells towards a TH2 phenotype. Using peptide-pulsed murine bone marrow-derived dendritic cells or murine fibroblasts expressing I-Ek with covalently attached antigenic peptide, we have assessed whether this sustained signaling influences the further effector subset differentiation. Using naïve or non-polarized, in vitro activated T cells, we observed that protein expression in trogocytosis positive (trog+) cells, but not trog– cells, is consistent with a pre-germinal center TFH phenotype (Bcl6+, PD-1+, ICOS+, CXCR5+, IL-21+). After adoptive transfer of FACS purified trog+ and trog– into wild type mice, cells recovered the trog+ recipients developed a pre-GC TFH phenotype in vivo. These findings suggest that trogocytosis-mediated signaling may contribute to TFH differentiation. Studies are underway to assess the functional characteristics of these cells. Funding Sources Suported by NIH/NIAID R15AI147034 and R03AI122167 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)