Trogocytosis-Mediated Intracellular Signaling in CD4+ T Cells Drives TH2-Associated Effector Cytokine Production and Differentiation

• Published in: The Journal of immunology (1950) 2019-05, Vol.202 (10), p.2873-2887
• Main Authors: Reed, Jim, Wetzel, Scott A.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1801577

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 TH2 phenotype. In vitro–polarized TH2 cells were found to be more efficient at performing trogocytosis than TH1 or nonpolarized CD4+ cells, whereas subsequent trogocytosis-mediated signaling induced TH2 differentiation in polarized TH1 and nonpolarized cells. Trogocytosis-positive CD4+ T cells generated in vivo also display a TH2 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 TH2-dominant immune response.