CD4+/CD8+ ratio

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]

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

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+ T cells by CD8 cytotoxic lymphocytes that productively infected cells.[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]

Decreased ratio with aging

A declining CD4+/CD8+ ratio is associated with ageing, and is an indicator of immunosenescence.[5][10] 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.[10] 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.[11][12] CD8+ cell recruitment of macrophages into adipose tissue can initiate a vicious cycle of further recruitment of both cell types.[12]

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][13] 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.[14] The increase in Treg with age results in suppressed immune response to infection, vaccination, and cancer, without suppressing the chronic inflammation associated with aging.[14]

See also

References
  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. PMC 4810120. PMID 26999211.
  2. Owen, Judith; Punt, Jenni; Stranford, Sharon (2013). Kuby Immunology. New York: W. H. Freeman and Company. p. 40.
  3. 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.
  4. 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.
  5. 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.
  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. PMC 5218901. PMID 28124011.
  7. 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.
  8. Kumar, Vinay (2012). Robbins Basic Pathology (9th ed.). p. 147. ISBN 9781455737871.
  9. Bruno G, Saracino A, Monno L, Angarano G (2017). "The Revival of an "Old" Marker: CD4/CD8 Ratio" (PDF). AIDS Reviews. 19 (2): 81–88. PMID 28182620.
  10. 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.
  11. 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.
  12. 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.
  13. 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. PMC 6685047. PMID 31403049.
  14. 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.
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