Myeloid molecular characteristics of human γδ T cells support their acquisition of tumor antigen-presenting capacity

Human T cells expressing gamma delta T cell receptor have a potential to show antigen-presenting cell-like phenotype and function upon their activation. However, the mechanisms that underlie the alterations in human gamma delta T cells remain largely unclear. In this study, we have investigated the molecular characteristics of human gamma delta T cells related to their acquisition of antigen-presenting capacity in comparison with activated alpha beta T cells. We found that activated gamma delta but not alpha beta T cells upregulated cell surface expression of a scavenger receptor, CD36, which seemed to be mediated by signaling through mitogen-activated protein kinase and/or NF-kappa B pathways. Confocal microscopical analysis revealed that activated gamma delta T cells can phagocytose protein antigens. Activated gamma delta T cells could induce tumor antigen-specific CD8(+) T cells using both apoptotic and live tumor cells as antigen resources. Furthermore, we detected that C/EBP alpha, a critical transcription factor for the development of myeloid-lineage cells, is expressed much higher in gamma delta T cells than in alpha beta T cells. These results unveiled the molecular mechanisms for the elicitation of antigen-presenting functions in gamma delta T cells and would also help designing new approaches for gamma delta T cell-mediated human cancer immunotherapy.