The cytokine storm is an intensified, dysregulated, tissue-injurious 
inflammatory response driven by cytokine and immune cell components. The 
cytokine storm during influenza virus infection, whereby the amplified innate 
immune response is primarily responsible for pulmonary damage, has been well 
characterized. Now we describe a novel event where virus-specific T cells induce 
a cytokine storm. The paramyxovirus pneumonia virus of mice (PVM) is a model of 
human respiratory syncytial virus (hRSV). Unexpectedly, when C57BL/6 mice were 
infected with PVM, the innate inflammatory response was undetectable until day 5 
postinfection, at which time CD8(+) T cells infiltrated into the lung, 
initiating a cytokine storm by their production of gamma interferon (IFN-γ) and 
tumor necrosis factor alpha (TNF-α). Administration of an immunomodulatory 
sphingosine-1-phosphate (S1P) receptor 1 (S1P1R) agonist significantly inhibited 
PVM-elicited cytokine storm by blunting the PVM-specific CD8(+) T cell response, 
resulting in diminished pulmonary disease and enhanced survival.
IMPORTANCE: A dysregulated overly exuberant immune response, termed a "cytokine 
storm," accompanies virus-induced acute respiratory diseases (VARV), is 
primarily responsible for the accompanying high morbidity and mortality, and can 
be controlled therapeutically in influenza virus infection of mice and ferrets 
by administration of sphingosine-1-phosphate 1 receptor (S1P1R) agonists. Here, 
two novel findings are recorded. First, in contrast to influenza infection, 
where the cytokine storm is initiated early by the innate immune system, for 
pneumonia virus of mice (PVM), a model of RSV, the cytokine storm is initiated 
late in infection by the adaptive immune response: specifically, by 
virus-specific CD8 T cells via their release of IFN-γ and TNF-α. Blockading 
these cytokines with neutralizing antibodies blunts the cytokine storm and 
protects the host. Second, PVM infection is controlled by administration of an 
S1P1R agonist.