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SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity.

Nature communications

Authors: Nicolas Huot, Philippe Rascle, Caroline Petitdemange, Vanessa Contreras, Christina M Stürzel, Eduard Baquero, Justin L Harper, Caroline Passaes, Rachel Legendre, Hugo Varet, Yoann Madec, Ulrike Sauermann, Christiane Stahl-Hennig, Jacob Nattermann, Asier Saez-Cirion, Roger Le Grand, R Keith Reeves, Mirko Paiardini, Frank Kirchhoff, Beatrice Jacquelin, Michaela Müller-Trutwin

Natural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that SIVagm infection induces the expansion of terminally differentiated NKG2a NK cells in secondary lymphoid organs displaying an adaptive transcriptional profile and increased MHC-E-restricted cytotoxicity in response to SIV Env peptides while expressing little IFN-γ. Such NK cell differentiation was lacking in SIVmac-infected macaques. Adaptive NK cells displayed no increased NKG2C expression. This study reveals a previously unknown profile of NK cell adaptation to a viral infection, thus accelerating strategies toward NK-cell directed therapies and viral control in tissues.

PMID: 33627642

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