The “ex Vivo” Patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR Expression Identify Acute/Early and Chronic/Late NK-Cell Activation States

To define a dynamic sequence of phenotypic changes related to early and late phases of NK-cell activation, we have analyzed by four-color flow cytometry the immunophenotype of normal blood NK-cells from 12 healthy individuals and compared it with those from 15 patients with acute viral infections and 15 patients with either chronic infections or tumors. Although a great interindividual variability was found, nonstimulated CD56+ NK-cells, present in normal blood samples, usually were CD2−/+lo, CD7+hi, HLA-DR−, CD11b+, CD38+, CD11a+hi, CD45RA+hi, and CD45RO−, the expression of CD11c and CD57 being heterogeneous and variable. Recently activated NK-cells, herein corresponding to NK-cells from patients with acute viral infections, displayed a pattern of expression of CD2/CD7 similar to that referred to above, but they typically showed higher levels of CD11a, CD38, and HLA-DR, as well as downregulation of CD11b and CD45RA, accompanied in some cases by coexpression of CD45RO; in addition, these NK-cells were CD11c+ and CD57−/+lo. Late-activated NK-cells, represented by NK-cells present in patients with chronic infections and tumors, converted into a CD2+hi/CD7−/+lo immunophenotype and expressed heterogeneously low levels of CD38 and CD11b; moreover, they were CD57+ and CD11c−/+. At this stage, most NK-cells had already reverted into their original CD45RA+/CD45RO−/HLA-DR− phenotype. In summary, we show that the patterns of expression of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR may help us to define the immunophenotypic profiles associated with early and late NK-cell activation phases in “in vivo” models.