Migration of cytotoxic lymphocytes in cell cycle permits local MHC-I dependent control of division at sites of viral infection (105.21)

Following virus infection, cytotoxic T lymphocytes (CTL) divide rapidly to eradicate the pathogen and prevent the establishment of persistence. The magnitude of an anti-viral CTL response is thought to be controlled by the initiation of a cell cycle program within lymphoid tissues. However, it is presently not known whether this division program proceeds during migration or is influenced locally at sites of viral infection. Here we demonstrate that anti-viral CTL remain in cell cycle while transiting to infected tissues. One third of virus-specific CTL within blood were found to be in cell cycle following infection with lymphocytic choriomeningitis virus (LCMV). Using two-photon microscopy, we revealed that effector CTL divided rapidly upon arrest in the virus-infected central nervous system (CNS) as well as meningeal blood vessels. We also observed that MHC I-dependent interactions (but not costimulation) influenced the division program by advancing effector CTL through stages of cell cycle. These results demonstrate that CTL are poised to divide in transit and that their numbers can be influenced locally at the site of infection through interactions with cells displaying cognate antigen.