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The CD4+/CD8+ ratio is the ratio of T helper cells (with the surface marker CD4) to cytotoxic T cells (with the surface marker CD8). Both CD4+ and CD8+ T cells contain several subsets.^[1]

The CD4+/CD8+ ratio in the peripheral blood of healthy adults and mice is about 2:1, and an altered ratio can indicate diseases relating to immunodeficiency or autoimmunity.^[2] An inverted CD4+/CD8+ ratio (namely, less than 1/1) indicates an impaired immune system.^[3][4][5]

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Scrutiny 7 5 6 – suite of web optimization tools. Obesity and dysregulated lipid metabolism in the liver leads to loss of CD4+, but not CD8+ cells, contributing to the induction of liver cancer.^[6]

Decreased ratio with infection[edit]

A reduced CD4+/CD8+ ratio is associated with reduced resistance to infection.^[7]

Patients with tuberculosis show a reduced CD4+/CD8+ ratio.^[7]

HIV infection leads to low levels of CD4⁺ T cells (lowering the CD4+/CD8+ ratio) through a number of mechanisms, including killing of infected CD4⁺. Acquired immunodeficiency syndrome (AIDS) is (by one definition) a CD4+ T cell count below 200 cells per µL. HIV progresses with declining numbers of CD4+ and expanding number of CD8+ cells (especially CD8+ memory cells), resulting in high morbidity and mortality.^[8] When CD4⁺ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections.^[3][4][5] Declining CD4+/CD8+ ratio has been found to be a prognostic marker of HIV disease progression.^[9]

COVID-19[edit]

In coronavirus disease 2019 (COVID-19) B cell, natural killer cell, and total lymphocyte counts decline, but both CD4+ and CD8+ cells decline to a far greater extent.^[10] Low CD4+ predicted greater likelihood of intensive care unit admission, and CD4+ cell count was the only parameter that predicted length of time for viral RNA clearance.^[10]

Decreased ratio with aging[edit]

A declining CD4+/CD8+ ratio is associated with ageing, and is an indicator of immunosenescence.^[5][11] Compared to CD4+ T-cells, CD8+ T-cells show a greater increase in adipose tissue in obesity and aging, thereby reducing the CD4+/CD8+ ratio.^[11] Amplication of numbers of CD8+ cells are required for adipose tissue inflammation and macrophage infiltration, whereas numbers of CD4+ cells are reduced under those conditions.^[12][13]Antibodies against CD8+ T-cells reduces inflammation associated with diet-induced obesity, indicating that CD8+ T-cells are an important cause of the inflammation.^[13] CD8+ cell recruitment of macrophages into adipose tissue can initiate a vicious cycle of further recruitment of both cell types.^[13]

Elderly persons commonly have a CD4+/CD8+ ratio less than one.^[9] A study of Swedish elderly found that a CD4+/CD8+ ratio less than one was associated with short-term likelihood of death.^[9]

Immunological aging is characterized by low proportions of naive CD8+ cells and high numbers of memory CD8+ cells,^[5][14] particularly when cytomegalovirus is present.^[5] Exercise can reduce or reverse this effect, when not done at extreme intensity and duration.^[5]

Both effector helper T cells (Th₁ and Th₂) and regulatory T cells (T_reg) cells have a CD4 surface marker, such that although total CD4+ T cells decrease with age, the relative percent of CD4+ T cells increases.^[15] The increase in T_reg with age results in suppressed immune response to infection, vaccination, and cancer, without suppressing the chronic inflammation associated with aging.^[15]

See also[edit]

References[edit]

1. ^Golubovskaya V, Wu L (2016). 'Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy'. Cancers. 8 (3): e36. doi:10.3390/cancers8030036. PMC4810120. PMID26999211.
2. ^Owen, Judith; Punt, Jenni; Stranford, Sharon (2013). Kuby Immunology. New York: W. H. Freeman and Company. p. 40.
3. ^ ^abMcBride JA, Striker R (2017). 'Imbalance in the game of T cells: What can the CD4/CD8 T-cell ratio tell us about HIV and health?'. PLOS Pathogens. 13 (11): e1006624. doi:10.1371/journal.ppat.1006624. PMC5667733. PMID29095912.
4. ^ ^abAiello A, Farzaneh F, Candore G, Caruso C, Davinelli S, Gambino CM, Ligotti ME, Zareian N, Accardi G (2019). 'Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention'. Frontiers in Immunology. 10: 2247. doi:10.3389/fimmu.2019.02247. PMC6773825. PMID31608061.
5. ^ ^abcdefTurner JE (2016). 'Is immunosenescence influenced by our lifetime 'dose' of exercise?'. Biogerontology. 17 (3): 581–602. doi:10.1007/s10522-016-9642-z. PMC4889625. PMID27023222.
6. ^Tran NL, Sitia G (2016). 'New players in non-alcoholic fatty liver disease induced carcinogenesis: lipid dysregulation impairs liver immune surveillance'. Hepatobiliary Surgery and Nutrition. 5 (6): 511–514. doi:10.21037/hbsn.2016.11.08. PMC5218901. PMID28124011.
7. ^ ^abYin Y, Qin J, Dai Y, Zeng F, Pei H, Wang J (2015). 'The CD4+/CD8+ Ratio in Pulmonary Tuberculosis: Systematic and Meta-Analysis Article'. Iranian Journal of Public Health. 44 (2): 185–193. PMC4401876. PMID25905052.
8. ^Kumar, Vinay (2012). Robbins Basic Pathology (9th ed.). p. 147. ISBN9781455737871.
9. ^ ^abcBruno G, Saracino A, Monno L, Angarano G (2017). 'The Revival of an 'Old' Marker: CD4/CD8 Ratio'. AIDS Reviews. 19 (2): 81–88. PMID28182620.
10. ^ ^abHuang W, Berube J, McNamara M, Saksena S, O'Gorman M (2020). 'Lymphocyte Subset Counts in COVID-19 Patients: A Meta-Analysis'. Cytometry Part A. 97 (8): 772–776. doi:10.1002/cyto.a.24172. PMC7323417. PMID32542842.
11. ^ ^abKalathookunnel Antony A, Lian Z, Wu H (2018). 'T Cells in Adipose Tissue in Aging'. Frontiers in Immunology. 9: 2945. doi:10.3389/fimmu.2018.02945. PMC6299975. PMID30619305.
12. ^Catalán V, Gómez-Ambrosi J, Rodríguez A, Frühbeck G (2013). 'Adipose tissue immunity and cancer'. Frontiers in Physiology. 4: 275. doi:10.3389/fphys.2013.00275. PMC3788329. PMID24106481.
13. ^ ^abcNishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R (2009). 'CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity'. Nature Medicine. 15 (8): 914–920. doi:10.1038/nm.1964. PMID19633658. S2CID5222216.
14. ^Tibbs TN, Lopez LR, Arthur JC (2019). 'The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging'. Microbial Cell. 6 (8): 324–334. doi:10.15698/mic2019.08.685. PMC6685047. PMID31403049.
15. ^ ^abJagger A, Shimojima Y, Goronzy JJ, Weyand CM (2014). 'Regulatory T cells and the immune aging process: a mini-review'. Gerontology. 60 (2): 130–137. doi:10.1159/000355303. PMC4878402. PMID24296590.

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