Date of Completion
Andrew Wiemer, Andrea Hubbard, Brian Aneskievich
University Scholar Major
Biological Phenomena, Cell Phenomena, and Immunity | Chemical and Pharmacologic Phenomena | Medical Cell Biology | Medical Immunology | Medical Pharmacology | Physiological Processes
Chronic antigenic stimulation leads to T cell exhaustion, which drastically dampens T cell effector functions. Upon exhaustion, T cells progressively lose their proliferative capacity, cytokine production, and cytotoxic effector functions against tumors. T cell exhaustion involves programmed cell death-1 (PD-1), which is an inhibitory co-stimulation receptor. Limited scope of studies has been done regarding impact of PD-1 expression on the effector functions of γδ T cells. In this study, we investigated expression of PD-1 and its impact on effector functions of human γδ T cells. When γδ T cells were stimulated with phosphoantigens (HMBPP and POM2-C-HMBP) and analyzed using flow cytometry, PD-1 expression peaked on day 5 and showed gradual decline thereafter. Treatment of γδ T cells with IL-2 without phosphoantigen stimulation can induce steady and continuous increase in PD-1 expression throughout the course of experiment. These results suggest that PD-1 may be expressed on highly primed γδ T cells. Upon concurrent dose response and time course experiments over 5-day period, we found that 10 µM POM2-C-HMBP treatment induced the maximum PD-1 expression on day 5. To demonstrate effect of anti-PD-1 monoclonal antibody on effector function of γδ T cells against tumor cells (K562), we quantified γδ T cells’ IFN-γ release by using ELISA and measured the absorbance. Contrary to our initial hypothesis, addition of anti-PD-1 monoclonal antibody did not appear to improve the effector function of γδ T cells, as difference in IFN-γ release among different treatment groups was not statistically significant. However, we found that increase in concentration of phosphoantigens increased effector functions of γδ T cells as demonstrated through increasing IFN-γ release.
Choi, MinJi; Wiemer, Andrew; Hubbard, Andrea; and Aneskievich, Brian, "Factors Involved In Suppression of Human Vγ9Vδ2 T-Lymphocytes And Impact of Checkpoint Blockades On The Effector Functions of Vγ9Vδ2 T-Lymphocytes" (2018). University Scholar Projects. 43.