Trying to Understand NK Cell Function in vivo Points towards a Severity Score for CVID Patients

Natural Killer (NK) cells were described 40 years ago as lymphoid cells exerting cytolytic activity against tumor cell lines in vitro (Herberman et al., 1975) and are accounted to the group of innate lymphoid cells. Functionally, they have been associated with anti-viral immunity (esp. herpesviridae) and tumor surveillance. However, NK cells have been less in the research focus compared to other components of the immune system (citations in Pubmed in 2015: ~2600 for NK cells compared to ~7100, ~14,600 and ~12,100 for B, T cells and macrophages, respectively). An isolated reduction of NK cells in humans has been suggested to be asymptomatic.Whether this notion somewhat reflects the inattentiveness towards NK cells or if NK cells in humans have only redundant functions in the immune system is still a matter of debate. Eric Vivier and colleagues hypothesized that the function of NK cells in humans might be revealed in immunocompromised subjects and report on a large cohort of patients with common variable immunodeficiency (CVID) registered in the French Registry (DEFI) (Ebbo et al., 2016). They stratified 457 CVID patients according to their NK cell numbers at study inclusion: roughly half of the patients had normal NK cell counts (N100/μl), one quarter of the patients had slightly reduced NK cell counts (50–99/μl) and almost one quarter had severely reduced NK cell numbers (b50/μl). CVID patients with severe NK cell lymphopenia exhibited a statistically significant increased rate of invasive bacterial infections defined as septicemia, pneumonia or meningitis: the frequency of invasive infections was 68.7% in severe NK lymphopenia, 60.2% in mild NK lymphopenia and 48.8% in patients with normal NK cell counts. However, there was no correlation of NK cell number and