CD8αα expression on NK cells is associated with different K562 and MOLT4 killing capabilities of PBMC and different involvement CD8pos and CD8neg subsets in anti-viral response

Abstract

Introduction. The CD8αα are present in a subset of T cells and NK cells, but its function is mostly unknown, as well as the role of CD8+ and CD8- NK cell subsets in physiological and pathological environments. Methods. We investigated 130 healthy individuals’ blood samples for the NK cell cytotoxicity against K562 and MOLT4 cell lines. We also analyzed patients after SarsCov2 infection and compared to healthy control. The NK cell phenotype and cytotoxicity were studied by the FACScan flow cytometer using BD monoclonal antibodies. Results. We confirmed that MOLT4 is significantly more resistant to the NK cell cytotoxicity compared to the “classical” K562. CD8+ NK cells are more effective at K562 killing compared to CD8- subsets. The correlation of lymphocyte levels with the specific K562 lysis was weaker for CD8- NK cell subsets (r = 0.37) than CD8+ NK cells (r = 0.45) or whole NK cells population (r = 0.46). However, we found that CD8+ NK cells mostly did not participate in the MOLT-4 killing. CD8- NK cells frequency correlates with MOLT4 lysis more significantly (r = 0.49) than CD8+ NK cells lymphocytes levels (r = 0.27) or whole NK cells population (r = 0.44). Also, we showed that HLA-DR and CD158a positive NK cell levels did not correlate with the MOLT4 and K562 killing, while HLA-DR and CD158a negative subsets levels did with the same significance as the whole NK cells population. Decreased of NK lymphocytes after SarsCov2 infection results to decrease NK population owing to CD8+NK decreased but not CD8neg. Conclusion. NK cell numbers determine NK cell cytotoxicity indirectly through the surface phenotype. CD8 expression on the NK cells is associated with the effective cytotoxicity against K562 but at the same time obstructs a response to MOLT4. CD8αα on NK cells might participate in HLA recognition or enhance response to HLA class-I negative target cells.