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

Abstract

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 H 2 phenotype. In vitro-polarized T H 2 cells were found to be more efficient at performing trogocytosis than T H 1 or nonpolarized CD4 + cells, whereas subsequent trogocytosis-mediated signaling induced T H 2 differentiation in polarized T H 1 and nonpolarized cells. Trogocytosis-positive CD4 + T cells generated in vivo also display a T H 2 phenotype in both TCR-transgenic and wild-type models. These findings suggest that trogocytosismediated signaling impacts CD4 + T cell differentiation and effector cytokine production and may play a role in augmenting or shaping a T H 2-dominant immune response.

High-Grade Serous Ovarian Tumor Cells Modulate NK Cell Function to Create an Immune-Tolerant Microenvironment

“…After coculture with OVCAR4 cells (15, 30, 60, 120 and 360min), CD9 was detected as early as 15min on NK-92 cells with a steady increase up to 360min ( Figure S6). These data are consistent with trogocytosis as previously reported in other systems (Reed and Wetzel, 2019).…”

Biting Off What Can Be Chewed: Trogocytosis in Health, Infection, and Disease

“…Finally, acquisition of membrane proteins via trogocytosis appears to be a driver of the T H 2 immune response. CD4 ϩ T cells that performed trogocytosis were associated with a T H 2 phenotype (90). Similarly, basophils that acquired peptide-MHC-II complexes via trogocytosis were able to stimulate peptide-specific naive CD4 ϩ T cells in vitro, in a manner consistent with a T H 2 phenotype (4).…”

Trogocytosis between Non-Immune Cells for Cell Clearance, and among Immune-Related Cells for Modulating Immune Responses and Autoimmunity

“…Recently, Aucher et al [ 57 ] reported that in vitro polarized CD4 + T cells were more efficiency in performing trogocytosis than Th1 or non-polarized CD4 + T cells. Interestingly, these trogocytosis-positive polarized CD4 + T cells generated in vivo displayed a Th2 phenotype [ 59 , 60 ]. These results indicate that trogocytosis-mediated signaling may play a crucial role in augmenting and shaping a Th2-dominant immune response.…”