Th1 and Th17 proinflammatory profile characterizes invariant natural killer T cells in virologically suppressed HIV+ patients with low CD4+/CD8+ ratio
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INTRODUCTION: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV-infected (HIV+) patients. METHODS: By flow cytometry, we studied iNKT cells from 54 HIV+ patients who started combined antiretroviral therapy and had undetectable viral load for more than 1 year. Twenty-five maintained a CD4/CD8 ratio less than 0.4, whereas 29 reached a ratio more than 1.1; 32 age-matched and sex-matched patients were healthy controls (CTR). RESULTS: Patients with low ratio had lower percentage of CD4 iNKT cells compared with patients with high ratio and higher CD8 iNKT cell percentage; double-negative iNKT cells were lower in HIV+ patients compared with CTR. Patients with low ratio had higher percentage of CD4 and double-negative iNKT cells expressing CD38 and HLA-DR compared with patients with high ratio. CD4 iNKT cells expressing PD-1 were higher in patients with CD4/CD8 ratio less than 0.4, whereas double-negative iNKT cells expressing PD-1 were lower compared with patients with ratio more than 1.1. Patients with low ratio had higher CD4 iNKT cells producing IL-17, CD8 iNKT cells producing IFN-γ, TNF-α or IFN-γ and TNF-α, and double-negative iNKT cells producing IL-17 or IL-17 and IFN-γ compared with CTR. Activated CD4 (or CD8) T cells correlated with activated CD4 (or CD8) iNKT cells, as well as the percentages of CD4 (or CD8) T cells expressing PD-1 was correlated to that of CD4 (or CD8) iNKT cells expressing PD-1. CONCLUSION: Low CD4/CD8 ratio despite effective combined antiretroviral therapy is associated with altered iNKT cell subsets, enhanced activation, and prominent Th1/Th17 proinflammatory profile.
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The amount of blood required to detect a reasonable number of rare cells according to Poisson statistics can be up to 50 mL, since both resting and stimulated cells have to be analyzed.
“Thus, the amount of blood required to detect a reasonable number of rare cells (according to Poisson statistics) can be up to 50 mL of blood, since both resting or stimulated cells have to be analyzed [98].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [98]
The Polychromatic flow cytometry section (page not provided) says that identifying rare circulating iNKT cells requires acquiring many cells and that up to 50 mL of blood was collected. The In-vitro stimulation section (page not provided) says both unstimulated and stimulated cells were analyzed. Our copy does not attribute the blood volume to Poisson statistics or explicitly say that analyzing both conditions is why 50 mL was collected. (LLM, conf=0.85)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531 · see citing works
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- Authors
- De Biasi, S., Bianchini, E., Nasi, M., Digaetano, M., Gibellini, L., Carnevale, G., Borghi, V., Guaraldi, G., Pinti, M., Mussini, C., & Cossarizza, A.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Cossarizza, Andrea
- ORCID
- Venue
- AIDS
- Published
- 2016-11-13
- Volume
- 30
- Issue
- 17
- Pages
- 2599-2610
- ISSN
- 0269-9370 (ISSN-L)
- OpenAlex
- W2525303244
- Cited by
- 39
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 5 · 2022: 1 · 2021: 13 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 5
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by
- Locations
- AIDS (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Keywords
- invariant natural killer T cells, HIV infection, virologically suppressed, CD4/CD8 ratio, PD-1, IL-17, interferon-gamma, TNF-α, CD38, HLA-DR, iNKT cell activation, antiretroviral therapy
- MeSH terms
- Sustained Virologic Response, Adult, Female, Flow Cytometry, Humans, Male, Middle Aged, CD4-Positive T-Lymphocytes, HIV Infections, CD4-CD8 Ratio, CD8-Positive T-Lymphocytes, Th1 Cells, Anti-Retroviral Agents, Natural Killer T-Cells, Th17 Cells
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