Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2Cnull Human Immunodeficiency Virus-Infected Individuals

Autor: Kayla A. Holder, Emilie M. Comeau, Michael D. Grant, Neva J. Fudge
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Human cytomegalovirus
Male
FcεRIγ
medicine.medical_treatment
Cell
PLZF
lcsh:QR1-502
Cytomegalovirus
HIV Infections
NKG2A
Lymphocyte Activation
lcsh:Microbiology
NKG2C
NKG2Cnull
0302 clinical medicine
Promyelocytic Leukemia Zinc Finger Protein
Receptor
Cytotoxicity
Antibody-dependent cell-mediated cytotoxicity
Coinfection
virus diseases
Cell Differentiation
Middle Aged
3. Good health
Killer Cells
Natural
Infectious Diseases
medicine.anatomical_structure
Cytokine
Cytomegalovirus Infections
Cytokines
Female
ADCC
NK Cell Lectin-Like Receptor Subfamily C
CD16
Adult
Human leukocyte antigen
Biology
GPI-Linked Proteins
Article
03 medical and health sciences
Virology
medicine
Humans
HCMV
Receptors
IgE
Receptors
IgG
Antibody-Dependent Cell Cytotoxicity
HIV
medicine.disease
CD2
030104 developmental biology
Immunology
030215 immunology
Zdroj: Viruses
Volume 11
Issue 3
Viruses, Vol 11, Iss 3, p 239 (2019)
ISSN: 1999-4915
Popis: Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate Fc&epsilon
RI&gamma
and promyelocytic leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV infection, but whether this affects NK cell acquisition of superior antibody-dependent function is unclear. Therefore, our objective was to investigate whether HCMV-driven NK cell differentiation is impaired in NKG2Cnull HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, Fc&epsilon
and PLZF expression) and functional (cytokine induction and cytotoxicity) properties were compared between HIV&ndash
infected NKG2Cnull and NKG2C-expressing groups. Cytokine production was compared following stimulation through natural cytotoxicity receptors or through CD16. Cytotoxicity was measured by anti-CD16-redirected lysis and by classical antibody-dependent cell-mediated cytotoxicity (ADCC) against anti-class I human leukocyte antigen (HLA) antibody-coated cells. Our data indicate highly similar HCMV-driven NK cell differentiation in HIV infection with or without NKG2C. While the fraction of mature (CD57pos) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and CD16 (p = 0.03) was significantly higher in NKG2Cnull HIV-infected individuals, there were no significant differences in NKG2A, Fc&epsilon
or PLZF expression. The general phenotypic and functional equivalency observed suggests NKG2C-independent routes of HCMV-driven NK cell differentiation, which may involve increased CD2 expression.
Databáze: OpenAIRE
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