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.
Lima
Margarida
M
Service of Clinical Hematology, Hospital Geral de Santo António, Porto, Portugal. mmc.lima@clix.pt
Almeida
Julia
J
dos Anjos Teixeira
Maria
M
Queirós
Maria Luís
ML
Justiça
Benvindo
B
Orfão
Alberto
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007239:Infections / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology; D013997:Time Factors; D014777:Virus Diseases / Q000276:immunology
D015703:Antigens, CD; D015415:Biomarkers