Characterization of the gamma delta T cell response to Amphotericin B

Abstract

Gamma delta T cells mediate a wide variety of functions within the host. Putative roles for these cells include tumor infiltration and clearance, pathogen detection and response, tissue repair and homeostasis, and augmentation or regulation of the inflammatory response. However, the precise roles gamma delta T cells play in the immune response to diseases and other stress-inducing states within the host are still unclear. Therefore, it is of interest to determine what types of molecules and signals are involved in the activation of these cells, altering their functional responses in disease states. As such, we screened numerous natural and synthetic compounds for their ability to activate bovine gamma delta T cells. Interestingly, a clinically approved antifungal drug, Amphotericin B, was found to prime the gamma delta T cells for activation. We demonstrate that Amphotericin B can utilize different receptors in a tissue-specific manner, making it a rather unique agonist for use as a therapeutic adjuvant. Amphotericin B was also able to act synergistically with other human and bovine gamma delta T cell agonists for enhanced activation of these cells. Furthermore, alternate formulations of the drug displayed different capabilities to stimulate gamma delta T cells. Interestingly, Amphotericin B was found to enhance the clearance of bacterial infections in mice, and the drug demonstrated potential as a potent vaccine adjuvant. Overall, Amphotericin B affects gamma delta T cell responses, and these cells are involved in a wide variety of immune responses. Therefore, Amphotericin B has the potential to be administered so as to manipulate the gamma delta T cell response for the benefit of the host during infectious disease.