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

Silvia S. Kang, Jasmin Herz, Jiyun V. Kim, Debasis Nayak, Phillip Stewart-Hutchinson, Michael L. Dustin, Dorian B. McGavern

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

After virus infection, cytotoxic T lymphocytes (CTLs) divide rapidly to eradicate the pathogen and prevent the establishment of persistence. The magnitude of an antiviral 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. We demonstrate that antiviral CTLs remain in cell cycle while transiting to infected tissues. Up to one third of virusspecific CTLs within blood were found to be in cell cycle after infection with lymphocytic choriomeningitis virus or vesicular stomatitis virus. Using two-photon microscopy, we found that effector CTL divided rapidly upon arrest in the virus-infected central nervous system as well as in 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 the cell cycle. These results demonstrate that CTLs 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.

Original languageEnglish (US)
Pages (from-to)747-759
Number of pages13
JournalJournal of Experimental Medicine
Volume208
Issue number4
DOIs
StatePublished - Apr 11 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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