Journal
RETROVIROLOGY
Volume 12, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12977-015-0191-3
Keywords
NK cells; Friend retrovirus; Regulatory T cells; IL-2 consumption; Treg suppression
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Funding
- University Hospital Essen (IFORES)
- Deutsche Forschungsgemeinschaft [TRR 60]
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Background: It is well established that effector T cell responses are crucial for the control of most virus infections, but they are often tightly controlled by regulatory T cells (Treg) to minimize immunopathology. NK cells also contribute to virus control but it is not known if their antiviral effect is influenced by virus-induced Tregs as well. We therefore analyzed whether antiretroviral NK cell functions are inhibited by Tregs during an acute Friend retrovirus infection of mice. Results: Selective depletion of Tregs by using the transgenic DEREG mouse model resulted in improved NK cell proliferation, maturation and effector cell differentiation. Suppression of NK cell functions depended on IL-2 consumption by Tregs, which could be overcome by specific NK cell stimulation with an IL-2/anti-IL-2 mAb complex. Conclusions: The current study demonstrates that virus-induced Tregs indeed inhibit antiviral NK cell responses and describes a targeted immunotherapy that can abrogate the suppression of NK cells by Tregs.
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