Trogocytosis-Mediated Intracellular Signaling in CD4 T Cells Drives T2-Associated Effector Cytokine Production and Differentiation.

CD4 T cells have been observed to acquire APC-derived membrane and membrane-associated molecules through trogocytosis in diverse immune settings. Despite this, the consequences of trogocytosis on the recipient T cell remain largely unknown. We previously reported that trogocytosed molecules on CD4 T cells engage their respective surface receptors, leading to sustained TCR signaling and survival after APC removal. Using peptide-pulsed bone marrow-derived dendritic cells and transfected murine fibroblasts expressing antigenic MHC:peptide complexes as APC, we show that trogocytosis-positive CD4 T cells display effector cytokines and transcription factor expression consistent with a T2 phenotype. In vitro-polarized T2 cells were found to be more efficient at performing trogocytosis than T1 or nonpolarized CD4 cells, whereas subsequent trogocytosis-mediated signaling induced T2 differentiation in polarized T1 and nonpolarized cells. Trogocytosis-positive CD4 T cells generated in vivo also display a T2 phenotype in both TCR-transgenic and wild-type models. These findings suggest that trogocytosis-mediated signaling impacts CD4 T cell differentiation and effector cytokine production and may play a role in augmenting or shaping a T2-dominant immune response.