Memory CD8 T cells in RSV infection: friend or foe?

Abstract

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory tract infection in infants and young children. CD8 T cells play a critical role in mediating viral clearance following an acute RSV infection. However the role of memory CD8 T cells in providing protection against RSV remains understudied. To generate high magnitude CD8 T cell memory in the absence of CD4 T cell memory and antibodies, we immunized naïve mice with dendritic cells pulsed with an RSV-derived peptide followed by a boost with a recombinant Listeria monocytogenes expressing the same RSV-derived epitope. Memory CD8 T cells significantly reduced viral titers following RSV challenge, but did so at the expense of increased airway dysfunction, weight loss, and mortality compared to controls. Importantly, the severe immunopathology and mortality observed was specific to the context of an RSV infection, as prime-boosted mice challenged with a recombinant influenza virus expressing the same RSV-derived epitope did not exhibit enhanced disease. The induction of a pro-inflammatory cytokine storm mediated by TNF-α and IFN-γ was observed in the serum of prime-boosted mice following RSV challenge. Additionally, RSV-specific memory CD8 T cells produced large amounts of IFN-γ locally within the lung, and adoptive transfer of wild-type but not IFN-γ-deficient memory CD8 T cells resulted in enhanced airway dysfunction and weight loss. Our results indicate that memory CD8 T cells are able to mediate protection against RSV infection. However, memory CD8 T cells acting alone in the absence of antibodies and memory CD4 T cells induce significant immunopathology and mortality through the induction of a systemic pro-inflammatory cytokine storm and local IFN-γ production.

Targeting CD40 enhances antibody- and CD8-mediated protection against respiratory syncytial virus infection

“…However, the contribution of memory CD8 T cells in providing protection against RSV re-infection remains to be fully understood in spite of their known importance in viral clearance 20,22,23 . Indeed, eliciting a robust memory CD8 T cell response is thought to be the key in developing a vaccine that can promote long-lived immunity against RSV 22,24 .CD40 and its ligand (CD40L) are a critical part of the adaptive immune system. In the adaptive immune response, antigen-presenting cells (APCs) must first be activated by an antigen with high affinity to MHC class I and/or II molecules on its surface.…”

“…However, the contribution of memory CD8 T cells in providing protection against RSV re-infection remains to be fully understood in spite of their known importance in viral clearance 20,22,23 . Indeed, eliciting a robust memory CD8 T cell response is thought to be the key in developing a vaccine that can promote long-lived immunity against RSV 22,24 .…”