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 |
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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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