CD8 T cells in in for the long haul

Like soldiers trained for a specific mission, CD8 T cells become tuned to fighting an exact pathogen but rather than bail out once the job is done, they stay in service fending off other invaders. CD8 T cells are a key part of the adaptive immune system, but also form part of the body’s innate immune system, becoming first responders to the calls of cytokines set off by a wide variety of infections scientists from Brown University said. Scientists tracked how CD8 T cells acquire both sensitivity for a specific virus – adaptive immunity ­ and the ability to respond to more general cytokine signals of infection – innate immunity. They infected mice with the LCMV virus and extracted CD8 T cells eight days later to observe them in culture with various cytokines, or in a control medium. While some T cells had become tuned to LCMV, others had not and those that had were more responsive to cytokines. In a further experiment, scientists infected knockout and control mice with LCMV twice to determine whether the protein STAT4 gave the T cells this cytokine responsiveness. Both sets of mice developed CD8 T cells that responded to LCMV after their first infection, but only mice with STAT4 produced an innate response via cytokine receptors during the second. Mice were then infected with MCMV to see how the CD8 T cells of LCMV-experienced mice responded to a new infection. Those who had already fought off LCMV responded rapidly because of the cytokines associated with the new invader. “Because of their experience, they got conditioned to now seeing innate cytokines in the way NK cells were seeing them at the beginning,” said Christine Biron, professor of medical science. “Once we’ve made these antigen-specific cells, then we have a subset of memory CD8 cells that still have the specificity for an antigen, but they are also changed now so their relationship with innate cytokines looks like NK cells.” It may be worthwhile pushing CD8 T cells harder when it comes to vaccine development as they have more flexibility in the kinds of activating receptors they can use and mimic some of the early responses of NK cells, added Biron. The study is published in mBio. CD8 T Cells in Innate Immune Responses: Using STAT4-Dependent but Antigen-Independent Pathways to Gamma Interferon during Viral Infection