Trogocytosis-mediated intracellular signaling in CD4⁺ T cells drives T_h2-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 T_H2 phenotype. In vitro–polarized T_H2 cells were found to be more efficient at performing trogocytosis than T_H1 or nonpolarized CD4⁺ cells, whereas subsequent trogocytosis-mediated signaling induced T_H2 differentiation in polarized T_H1 and nonpolarized cells. Trogocytosis-positive CD4⁺ T cells generated in vivo also display a T_H2 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 T_H2-dominant immune response.