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.

Age-dependent Immune Response to the Biontech/Pfizer BNT162b2 Coronavirus Disease 2019 Vaccination.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to the development of various vaccines. Real-life data on immune responses elicited in the most vulnerable group of vaccinees older than age 80 years old are still underrepresented despite the prioritization of the elderly in vaccination campaigns. METHODS: We conducted a cohort study with 2 age groups, young vaccinees below the age of 60 years and elderly vaccinees over the age of 80 years, to compare their antibody responses to the first and second dose of the BNT162b2 coronavirus disease 2019 vaccination. RESULTS: Although the majority of participants in both groups produced specific immunoglobulin G antibody titers against SARS-CoV-2 spike protein, titers were significantly lower in elderly participants. Although the increment of antibody levels after the second immunization was higher in elderly participants, the absolute mean titer of this group remained lower than the <60 years of age group. After the second vaccination, 31.3% of the elderly had no detectable neutralizing antibodies in contrast to the younger group, in which only 2.2% had no detectable neutralizing antibodies. CONCLUSIONS: Our data showed differences between the antibody responses raised after the first and second BNT162b2 vaccination, in particular lower frequencies of neutralizing antibodies in the elderly group. This suggests that this population needs to be closely monitored and may require earlier revaccination and/or an increased vaccine dose to ensure stronger long-lasting immunity and protection against infection.