Antigen-specific NK cell memory

Do NK cells have memory? New study in Nature Immunology suggests they do. 

This study was done on rhesus macaques. Purified NK cells were sorted from spleen, liver or blood. Autologous, virus infected or antigen-pulsed DCs were used as targets. Control DCs were either uninfected or mismatched antigen-pulsed.

Initially, the authors observed that purified spleen (c) or hepatic (d) NK cells from SHIV-infected hosts showed cytotoxic response to Gag and Env, but not OVA pulsed autologous DCs.

Similarly, purified splenic NK cells derived from SIV-infected hosts showed antigen-specific cytotoxicity (a, b). Interestingly, blood derived NK cells showed no cytotoxic activity against antigen-pulsed DCs (c).   

Finally, the authors showed that splenic (c) and hepatic (d) NK cells derived from hosts vaccinated 5 years earlier displayed vaccine-matching antigen-specific DCs lysis. Here too, blood derived NK cells showed minimal antigen-pulsed DCs lysis (e).

Additional results indicated that NK-mediated lysis of antigen-pulsed DCs were mediated via NKG2C or NKG2A pathways. These NK receptors recognize MHC class I molecules loaded with leader peptides derived from other endogenous MHC molecules. However, it is not clear how this mechanism confers exogenous antigen-specific memory to NK cells.

In summary, these results suggest that NK cells could mount antigen-specific memory response. 

David Usharauli