NKG2Cpos NK Cells Regulate the Expansion of Cytomegalovirus-Specific CD8 T Cells.
J Immunol
; 204(11): 2910-2917, 2020 06 01.
Article
em En
| MEDLINE
| ID: mdl-32284334
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Linfócitos T
/
Infecções por Citomegalovirus
/
Linfócitos T CD8-Positivos
/
Citomegalovirus
Limite:
Adult
/
Animals
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article