Imaging CD8+ T cells during diverse viral infections.

CD8⁺ T cells play a critical role in host defense against pathogens and tumors. Much of our current knowledge of the activation and subsequent effector activities of CD8⁺ T cells has been gained using ex vivo approaches examining the T cell population en masse for surface phenotype, activation status and the production of effector molecules. Thus, the precise behaviors and diversity of individual CD8⁺ T cells responding to virus infection in vivo have not been extensively explored, leaving many unanswered questions relevant to the rational design of antiviral vaccines and therapeutics. Recently, intravital multiphoton microscopy (MPM) has been used to image CD8⁺ T cell priming after infection with disparate viral pathogens ranging from small RNA viruses encoding few proteins to DNA viruses producing hundreds of viral proteins (many immunomodulatory). After priming, effector CD8⁺ T cells have been visualized in virus-infected tissue, both during primary infection and after transitioning to tissue resident memory cells (T_RM). Here, I highlight recent advances in our understanding of antiviral CD8⁺ T cell responses revealed through intravital MPM.