The activation of bystander CD8+ T cells and their roles in viral infection

During viral infections, significant numbers of T cells are activated in a T cell receptor-independent and cytokine-dependent manner, a phenomenon referred to as “bystander activation.” Cytokines, including type I interferons, interleukin-18, and interleukin-15, are the most important factors that induce bystander activation of T cells, each of which plays a somewhat different role. Bystander T cells lack specificity for the pathogen, but can nevertheless impact the course of the immune response to the infection. For example, bystander-activated CD8 + T cells can participate in protective immunity by secreting cytokines, such as interferon-γ. They also mediate host injury by exerting cytotoxicity that is facilitated by natural killer cell-activating receptors, such as NKG2D, and cytolytic molecules, such as granzyme B. Interestingly, it has been recently reported that there is a strong association between the cytolytic function of bystander-activated CD8 + T cells and host tissue injury in patients with acute hepatitis A virus infection. The current review addresses the induction of bystander CD8 + T cells, their effector functions, and their potential roles in immunity to infection, immunopathology, and autoimmunity. Viral infection: Inciting an immunological mob Immune cells that are non-specifically activated during infection can offer protection, but may also inflict collateral damage on infected patients. T cells normally mount an antigen-specific immune response, but certain T cells can become stimulated during viral infection without selective activation by a particular antigen. Tae-Shin Kim and Eui-Cheol Shin at KAIST in Daejon, South Korea, have reviewed current insights into this ‘bystander activation’ phenomenon. They explore how the immune response to viruses such as influenza and hepatitis A produces molecular signals that induce bystander activation of ‘killer’ T cells. In some scenarios, this leads to stronger immune protection, but these cells can also damage host tissues, or contribute to disease progression. Modulating this nonspecific response could prove valuable in managing the severity of viral disease.