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] Conversely, an increased CD4+/CD8+ ratio corresponds to increased immune function.[6]
Obesity and dysregulated lipid metabolism in the liver leads to loss of CD4+, but not CD8+ cells, contributing to the induction of liver cancer.[7] Regulatory CD4+ cells decline with expanding visceral fat, whereas CD8+ T-cells increase.[8]
Decreased ratio with infection
editA reduced CD4+/CD8+ ratio is associated with reduced resistance to infection.[9]
Patients with tuberculosis show a reduced CD4+/CD8+ ratio.[9]
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.[10] 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.[11]
COVID-19
editThis section may be confusing or unclear to readers. (June 2021) |
In COVID-19 B cell, natural killer cell, and total lymphocyte counts decline, but both CD4+ and CD8+ cells decline to a far greater extent.[12] 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.[12]
Decreased ratio with aging
editA declining CD4+/CD8+ ratio is associated with ageing, and is an indicator of immunosenescence.[5][13] 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.[13] 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.[14][15] Antibodies against CD8+ T-cells reduces inflammation associated with diet-induced obesity, indicating that CD8+ T-cells are an important cause of the inflammation.[15] CD8+ cell recruitment of macrophages into adipose tissue can initiate a vicious cycle of further recruitment of both cell types.[15]
Elderly persons commonly have a CD4+/CD8+ ratio less than one.[11] A study of Swedish elderly found that a CD4+/CD8+ ratio less than one was associated with short-term likelihood of death.[11]
Immunological aging is characterized by low proportions of naive CD8+ cells and high numbers of memory CD8+ cells,[5][16] 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 (Treg) cells have a CD4 surface marker, such that although total CD4+ T cells decrease with age, the relative percent of CD4+ T cells increases.[17] The increase in Treg with age results in suppressed immune response to infection, vaccination, and cancer, without suppressing the chronic inflammation associated with aging.[17]
See also
editReferences
edit- ^ 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. PMC 4810120. PMID 26999211.
- ^ Owen, Judith; Punt, Jenni; Stranford, Sharon (2013). Kuby Immunology. New York: W. H. Freeman and Company. p. 40.
- ^ a b McBride 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. PMC 5667733. PMID 29095912.
- ^ a b Aiello 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. PMC 6773825. PMID 31608061.
- ^ a b c d e f Turner JE (2016). "Is immunosenescence influenced by our lifetime "dose" of exercise?". Biogerontology. 17 (3): 581–602. doi:10.1007/s10522-016-9642-z. PMC 4889625. PMID 27023222.
- ^ Bradshaw PC, Seeds WA, Curtis WM (2020). "COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm". Oxidative Medicine and Cellular Longevity. 2020: 6401341. doi:10.1155/2020/6401341. PMC 7519203. PMID 33014275.
- ^ 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. PMC 5218901. PMID 28124011.
- ^ Krüger K, Eder K, Ringseis R (2014). "Immune and Inflammatory Signaling Pathways in Exercise and Obesity". Am J Lifestyle Med. 10 (4): 268–279. doi:10.1177/1559827614552986. PMC 6125063. PMID 30202282.
- ^ a b Yin 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. PMC 4401876. PMID 25905052.
- ^ Kumar, Vinay (2012). Robbins Basic Pathology (9th ed.). Elsevier Health Sciences. p. 147. ISBN 9781455737871.
- ^ a b c Bruno G, Saracino A, Monno L, Angarano G (2017). "The Revival of an "Old" Marker: CD4/CD8 Ratio". AIDS Reviews. 19 (2): 81–88. PMID 28182620.
- ^ a b Huang 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. PMC 7323417. PMID 32542842.
- ^ a b Kalathookunnel 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. PMC 6299975. PMID 30619305.
- ^ 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. PMC 3788329. PMID 24106481.
- ^ a b c Nishimura 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. PMID 19633658. S2CID 5222216.
- ^ 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 (inactive 2024-11-02). PMC 6685047. PMID 31403049.
{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link) - ^ a b Jagger 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. PMC 4878402. PMID 24296590.