RIG-I receptor regulation of T cell immunity during virus infection (P4361)

Abstract West Nile Virus (WNV) is an RNA virus that is the leading cause of mosquito-borne encephalitis in the United States. Recently, we demonstrated that MAVS, the central adaptor molecule of the RIG-I like receptor (RLR) signaling pathway, is essential role in programming innate and adaptive immune defenses to control WNV infection. However, the role of the individual RLRs in directing immunity during virus infection has not been clearly defined. WNV infection of Lgp2-/- mice showed increased mortality which corresponded to enhanced virus replication and reduced antigen-specific CD8+ T cells in the CNS at late times during infection. While LGP2 was determined to be non-essential in innate immune responses to WNV infection, LGP2 was required for controlling antigen-specific CD8+ T cell survival and effector functions during virus infection. Adoptive transfer studies of WT and Lgp2-/- CD8+ T cells into Rag-/- mice demonstrated that LGP2 functions in a cell-intrinsic manner to regulate T cell sensitivity to CD95-mediated cell death. Biochemical studies showed that LGP2 expression in CD8+ T cells is regulated through crosstalk between the T cell receptor signaling and interferon signaling pathways. Mechanisms by which LGP2 regulates extrinsic apoptosis signaling and T cell survival will be discussed. Overall, these studies demonstrate a novel for LGP2 in regulating T cell immunity and reveals a broader role for RLRs in programming adaptive immune responses during virus infection.