Mechanisms underlying T cell guided innate immunity after inhalation of Staphylococcus enterotoxin A (SEA) (173.1)

Abstract

Abstract Inhalation of Staphylococcus aureus enterotoxin A (SEA) in mice induces strong pulmonary inflammation marked by vascular permeability and alveolitis, thereby modeling aspects of lung injury in humans. After SEA inhalation CD8+Vβ3+ T cells robustly expand but the early events of this response in the lung are unclear. Our new data show that Vβ3+ T cells are activated quickly after SEA inhalation since CD69 and the high affinity IL-2 receptor α-chain (CD25) were upregulated by 3 hours. This coincided with several changes in the innate immune system including recruitment of neutrophils, monocytes and NK cells into the lung, and imprinting an activation phenotype on macrophages. Importantly, in the absence of T cells all of these effects were abrogated. As a way to understand how T cells condition innate immunity, we analyzed cytokine production and found an unexpected role for TCRαβ T cells promoting IL-17 secretion by TCRγδ T cells. We demonstrated that TCRγδ cells did not produce IL-17 when tested in TCRβ-/- mice. Currently, we are defining how TCRγδ cells are induced to synthesize IL-17 by the TCRαβ cells. In sum, TCRαβ T cells mediate pro-inflammatory responses, not only as a direct source of cytokines, but also by guiding the recruitment and activation of innate cells. Thus, our data show role reversal between the adaptive immune and innate immune system.