NKG2Cpos NK Cells Regulate the Expansion of Cytomegalovirus-Specific CD8 T Cells.

Infection with the human CMV associates with phenotypic alterations in lymphocyte subsets. A highly reproducible finding in CMV-seropositive individuals is an expansion of NKG2Cpos NK cells. In this study, we analyzed if the altered NK cell compartment in CMV-seropositive human donors may affect CMV-specific CD8 T cells. Resting CMV-specific CD8 T cells were terminally differentiated and expressed high levels of the NKG2C ligand HLA-E. Activation of CMV-specific CD8 T cells with the cognate Ag further increased HLA-E expression. In line with a negative regulatory effect of NKG2Cpos NK cells on HLA-Ehigh CD8 T cells, depletion of NKG2Cpos NK cells enhanced Ag-specific expansion of CMV-specific CD8 T cells in vitro. In turn, the activation of NK cells in coculture with CMV-specific CD8 T cells promoted a selective loss of HLA-Ehigh CD8 T cells. To test if NKG2Cpos NK cells can target HLA-Ehigh CD8 T cells, Jurkat T cells with and without stabilized HLA-E on the surface were used. NKG2Cpos NK cells stimulated with HLA-Ehigh Jurkat cells released higher levels of Granzyme B compared with NKG2Cneg NK cells and NKG2Cpos NK cells stimulated with HLA-Elow Jurkat cells. Moreover, intracellular levels of caspase 3/7 were increased in HLA-Ehigh Jurkat cells compared with HLA-Elow Jurkat cells, consistent with higher rates of apoptosis in HLA-Ehigh T cells in the presence of NKG2Cpos NK cells. Our data show that NKG2Cpos NK cells interact with HLA-Ehigh CD8 T cells, which may negatively regulate the expansion of CMV-specific CD8 T cells upon activation.

Multicenter Performance Evaluation of Elecsys Anti-HBc II, Anti-HCV II, HIV combi PT, HBsAg II, and Syphilis Immunoassays.

BACKGROUND: The WHO recommends mandatory serological testing of blood donors for hepatitis B virus, hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis. We evaluated the performance of Elecsys® infectious disease immunoassays against commercially available comparator assays. METHODS: Prospective, routine, anonymized patient or donor samples (n = 8,821) were analyzed at three German sites using Elecsys antihepatitis B core antigen (Anti-HBc II), Anti-HCV II, HIV combi PT, hepatitis B surface antigen (HBsAg II), and Syphilis immunoassays (cobas e 411 analyzer) versus ARCHITECT comparator assays. RESULTS: The Elecsys immunoassays demonstrated comparable sensitivity (≤ 1.54% difference) and equivalent specificity (≤ 0.63% difference) to the respective ARCHITECT comparator assays. Overall sensitivity for the Elecsys and ARCHITECT infectious disease panels was 99.78% vs. 99.40%, respectively, and overall specificity was 99.74% vs. 99.80%, respectively. CONCLUSIONS: The Elecsys infectious disease immunoassays demonstrated high sensitivity and specificity, which were similar to comparator assays, supporting their suitability for routine laboratory practice.