Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8 + T-cell immunity

Philipp A. Lang, Karl S. Lang, Haifeng C. Xu, Melanie Grusdat, Ian A. Parish, Mike Recher, Alisha R. Elford, Salim Dhanji, Namir Shaabani, Charles W. Tran, Dilan Dissanayake, Ramtin Rahbar, Magar Ghazarian, Anne Brüstle, Jason Fine, Peter Chen, Casey T. Weaver, Christoph Klose, Andreas Diefenbach, Dieter HäussingerJames R. Carlyle, Susan M. Kaech, Tak W. Mak, Pamela S. Ohashi*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

255 Citations (Scopus)


Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease.Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus.NK cell-deficient (Nfil3 -/-, E4BP4 -/-)mice exhibited a higher virus-specific T-cell response. In addition, NK cell depletion caused enhanced T-cell immunity in WT mice, which led to rapid virus control and prevented chronic infection in lymphocytic choriomeningitis virus clone 13- and reduced viral load in DOCILEinfected animals. Further experiments showed that NKG2D triggered regulatory NK cell functions, which were mediated by perforin, and limited T-cell responses. Therefore,we identified an important role of regulatory NK cells in limiting T-cell immunity during virus infection.

Original languageEnglish
Pages (from-to)1210-1215
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
Publication statusPublished - 24 Jan 2012
Externally publishedYes


  • Effector T cells
  • NK cell activation
  • Regulatory innate immunity
  • Virus elimination
  • Virus persistence


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