Medical Microbiology and Immunology

, Volume 204, Issue 3, pp 335–344 | Cite as

The specific NK cell response in concert with perforin prevents CD8+ T cell-mediated immunopathology after mouse cytomegalovirus infection

  • Jurica Arapović
  • Maja Arapović
  • Mijo Golemac
  • Luka Traven
  • Jelena Tomac
  • Dijana Rumora
  • Edvard Ražić
  • Astrid Krmpotić
  • Stipan JonjićEmail author
Original Investigation
Part of the following topical collections:
  1. Cytomegalovirus


Natural killer (NK) and CD8+ T cells play a crucial role in the control of mouse cytomegalovirus (MCMV) infection. These effector cells exert their functions by releasing antiviral cytokines and by cytolytic mechanisms including perforin activation. In addition to their role in virus control, NK cells play an immunoregulatory role since they shape the CD8+ T cell response to MCMV. To investigate the role of perforin-dependent cytolytic mechanism in NK cell modulation of CD8+ T cell response during acute MCMV infection, we have used perforin-deficient C57BL/6 mice (Prf1−/−) and have shown that virus control by CD8+ T cells in Prf1−/− mice is more efficient if NK cells are activated by the engagement of the Ly49H receptor with the m157 MCMV protein. A lack of perforin results in severe liver inflammation after MCMV infection, which is characterized by immunopathological lesions that are more pronounced in Prf1−/− mice infected with virus unable to activate NK cells. This immunopathology is caused by an abundant infiltration of activated CD8+ T cells. The depletion of CD8+ T cells has markedly reduced pathohistological lesions in the liver and improved the survival of Prf1−/− mice in spite of an increased viral load. Altogether, the results of our study suggest that a lack of perforin and absence of the specific activation of NK cells during acute MCMV infection lead to an unleashed CD8+ T cell response that is detrimental for the host.


Mouse cytomegalovirus (MCMV) CD8+ T cells Immunopathology Perforin NK cells Ly49H 



We thank Jelena Boneta for performing immunofluorescent CD8+ T cell staining, Prof. Nives Jonjic for help with pathohistological analysis, and Dr. Felix M. Wensveen for discussion. J. A. is supported by the Federal Ministry of Education and Science, Bosnia and Herzegovina. This work has been supported in part by Croatian Science Foundation under the project 7132 (to AK) and by the University of Rijeka under the projects (to SJ) and (to AK).

Conflict of interest

The authors declare no financial or commercial conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Jurica Arapović
    • 1
    • 2
  • Maja Arapović
    • 1
  • Mijo Golemac
    • 1
  • Luka Traven
    • 3
  • Jelena Tomac
    • 1
  • Dijana Rumora
    • 1
  • Edvard Ražić
    • 1
  • Astrid Krmpotić
    • 1
  • Stipan Jonjić
    • 1
    Email author
  1. 1.Department of Histology and Embryology, Faculty of MedicineUniversity of RijekaRijekaCroatia
  2. 2.Faculty of MedicineUniversity of MostarMostarBosnia and Herzegovina
  3. 3.Department of Environmental Medicine, Faculty of MedicineUniversity of RijekaRijekaCroatia

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