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Generation of Natural Killer Cells from Human Expanded Potential Stem Cells
Published on: January 13, 2023
NK cells generate memory-type responses to human cytomegalovirus-infected fibroblasts
Nicholas Newhook1, Neva Fudge1, Michael Grant1
1Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Insights
Human cytomegalovirus (HCMV) infection prompts a memory-like response in natural killer (NK) cells, enhancing their proliferation and function. This NK cell memory may be partly independent of NKG2C expression.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Natural killer (NK) cells are crucial for innate immunity, targeting abnormal cells.
- Human cytomegalovirus (HCMV) infection is known to induce specific NK cell subset expansions.
- The existence of pathogen-specific NK cell memory is an emerging area of research.
Purpose of the Study:
- To investigate whether human NK cells mount a memory-type response against HCMV.
- To compare NK cell proliferation, cytotoxicity, and cytokine production in response to HCMV infection.
- To explore the role of NKG2C expression in HCMV-specific NK cell responses.
Main Methods:
- Co-culture of NK cells from HCMV-seropositive and seronegative individuals with HCMV-infected or uninfected MRC-5 cells.
- Assessment of NK cell proliferation, natural cytotoxicity against K562 cells, and interferon-gamma (IFN-γ) production.
- Analysis of NKG2C+ and NKG2C- NK cell subsets.
Main Results:
- NK cells from HCMV-seropositive individuals showed significantly increased proliferation upon encountering HCMV-infected cells compared to uninfected cells.
- Natural cytotoxicity and IFN-γ production were enhanced in NK cells from HCMV-seropositive donors after exposure to HCMV-infected cells.
- Both NKG2C+ and NKG2C- NK cells proliferated, suggesting a partly NKG2C-independent memory response.
Conclusions:
- Human NK cells can exhibit a memory-type response to HCMV infection.
- This response involves enhanced proliferation, cytotoxicity, and cytokine production.
- The observed NK cell memory against HCMV is at least partially independent of NKG2C expression.
Abstract:
Natural killer (NK) cells are cytotoxic lymphocytes that selectively respond against abnormal cells. Human cytomegalovirus (HCMV) infection causes expansion of NKG2C+ CD57+ NK cells in vivo and NKG2C+ NK cells proliferate when cultured with HCMV-infected cells. This raises the possibility of an NK-cell subset selectively responding against a specific pathogen and accruing memory. To test this possibility, we compared proliferation, natural cytotoxicity and interferon-γ (IFN-γ) production of NK cells from HCMV-seropositive and HCMV-seronegative individuals co-cultured with HCMV-infected or uninfected MRC-5 cells. There was no significant difference in proliferation of NK cells from HCMV-seropositive or seronegative individuals against uninfected MRC-5 cells, but significantly more NK cells from the HCMV-seropositive group proliferated in response to HCMV-infected MRC-5 cells. Natural cytotoxicity of NK cells against K562 cells increased following co-culture with HCMV-infected versus uninfected MRC-5 only for the HCMV-seropositive group. After co-culture with HCMV-infected MRC-5 cells, proliferating NK cells from HCMV-seropositive donors selectively produced IFN-γ when re-exposed to HCMV-infected MRC-5 cells. Both NKG2C+ and NKG2C- NK cells proliferated in co-culture with HCMV-infected MRC-5 cells, with the fraction of proliferating NKG2C+ NK cells directly correlating with the circulating NKG2C+ fraction. These data illustrate an at least partly NKG2C-independent human NK-cell memory-type response against HCMV.
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