Priming of γδ T cells (52.4)

Abstract

Abstract We have begun to elucidate the role of γδ T cells in innate immunity. Purified human and bovine γδ T cells display a subtle activation, akin to priming, in response to a wide variety of pathogen associated molecular patterns (PAMPs) such as lipopolysaccharide and peptidoglycan. A primed γδ T cell displays an enhanced response to downstream secondary signals compared to resting cells, but is not overtly activated. The signature response of a primed γδ T cell include increases in Mip1α, GM-CSF, and IL-2Rα gene and protein expression, that renders them more sensitive to IL-2. Priming is distinct from overt activation by known TCR agonists in that upregulation of IFNγ and TNFα, the signature of an activated γδ T cell, are rarely detected. Priming has also been detected in vivo in γδ, but not αβ, T cells derived from the gut mucosa of Salmonella infected calves. In an effort to manipulate γδ T cells to provide an innate protective response, we have identified compounds and herbal products that mimic the priming activation of PAMPs on γδ T cells. Treatment of bovine calves with one of the plant extracts protects against Salmonella-induced enterocolitis. γδ T cell priming may be a critical step in innate immune protection and clearance, especially for pathogens that invade mucosal surfaces, where the majority of γδ T cells are found.