CD4+/CD8+ ratio

The CD4+/CD8+ ratio measures the ratio of T helper cells to cytotoxic T cells. 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.[1] An inverted CD4+/CD8+ ratio (namely, less than 1/1) indicates an impaired immune system.[2] A reduced CD4+/CD8+ ratio is associated with reduced resistance to infection.[3] Patients with tuberculosis show a reduced CD4+/CD8+ ratio.[3]

A declining CD4+/CD8+ ratio is associated with ageing, and is an indicator of immunosenescence.[4][5] A study of elderly humans showed the highest expansion of cytotoxic T cells among those with cytomegalovirus.[5] In obese adipose tissue, pro-inflammatory CD8+ cells increase and recruit macrophages,[6] predominating over anti-inflammatory CD4+ cells.[7]

HIV infection leads to low levels of CD4+ T cells (lowering the CD4+/CD8+ ratio) through a number of mechanisms, including pyroptosis of abortively infected CD4 T cells,[8] apoptosis of productively infected CD4 T cells,[9] and killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize productively infected cells.[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. Assessing the levels of viable CD4+/CD8+ T cells in HIV-infected human lymphoid tissues using flow cytometry is shown here (Figure S5).[11] People living with HIV who have a higher CD4/CD8 ratio may have a lower HIV reservoir.[12] A website called Game of T cells (gameoftcells.medicine.wisc.edu) offers monthly blogs about clinical conditions associated with altered CD4/CD8 ratios and a possible relationship between the HIV reservoir and the CD4/CD8 ratio.

A high CD4+/CD8+ ratio is associated with patient survival in non-small-cell lung carcinoma.[13] The opposite may be true for the cells infiltrating glioma,[14] but it is unknown whether in all cases the bias in CD4/CD8 in an affected tumor or organ is reflected in the blood.

See also

References

  1. ↑ Owen, Judith; Punt, Jenni; Stranford, Sharon (2013). Kuby Immunology. New York: W. H. Freeman and Company. p. 40.
  2. ↑ Luz Correa B, Ornaghi AP, Cerutti Muller G, Engroff P, Pestana Lopes R, Gomes da Silva Filho I, Bosch JA, Bonorino C, Bauer ME (2014). "The inverted CD4:CD8 ratio is associated with cytomegalovirus, poor cognitive and functional states in older adults". Neuroimmunomodulation. 21 (4): 206–212. doi:10.1159/000356827. PMID 24504177.
  3. 1 2 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.
  4. ↑ Serrano-Villar S, Moreno S, Fuentes-Ferrer M, Sánchez-Marcos C, Avila M, Sainz T, de Villar NG, Fernández-Cruz A, Estrada V (2014). "The CD4:CD8 ratio is associated with markers of age-associated disease in virally suppressed HIV-infected patients with immunological recovery". HIV Medicine. 15 (1): 40–49. doi:10.1111/hiv.12081. PMID 24007533.
  5. 1 2 Hadrup SR, Strindhall J, Køllgaard T, Seremet T, Johansson B, Pawelec G, thor Straten P, Wikby A (2006). "Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly". Journal of Immunology. 176 (4): 2645–2653. doi:10.4049/jimmunol.176.4.2645. PMID 16456027.
  6. ↑ 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.
  7. ↑ Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker DJ, Engleman E, Winer D, Dosch HM (2009). "Normalization of obesity-associated insulin resistance through immunotherapy". Nature Medicine. 15 (8): 921–929. doi:10.1038/nm.2001. PMC 3063199. PMID 19633657.
  8. ↑ Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C. (2014). "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature. 505 (7484): 509–514. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.
  9. ↑ Cooper A, García M, Petrovas C, Yamamoto T, Koup RA, Nabel GJ (June 20, 2013). "HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration". Nature. 498 (7454): 376–9. doi:10.1038/nature12274. PMID 23739328.
  10. ↑ Kumar, Vinay (2012). Robbins Basic Pathology (9th ed.). p. 147. ISBN 9781455737871.
  11. ↑ Galloway NL, Doitsh G, Monroe KM, Yang Z, Muñoz-Arias I, Levy DN, Greene WC (2015). "Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-TissueDerived CD4 T Cells". Cell Rep. 12: 1555–63. doi:10.1016/j.celrep.2015.08.011. PMC 4565731. PMID 26321639. Retrieved March 15, 2017.
  12. ↑
  13. ↑ Jackute J, Zemaitis M, Pranys D, Sitkauskiene B, Miliauskas S, Bajoriunas V, Lavinskiene S, Sakalauskas R (2015). "The prognostic influence of tumor infiltrating Foxp3(+)CD4(+), CD4(+) and CD8(+) T cells in resected non-small cell lung cancer". JOURNAL OF INFLAMMATION. 12: 63. doi:10.1186/s12950-015-0108-x. PMC 4657296. PMID 26604855.
  14. ↑ Han S, Zhang C, Li Q, Dong J, Liu Y, Huang Y, Jiang T, Wu A (2014). "Tumour-infiltrating CD4(+) and CD8(+) lymphocytes as". British Journal of Cancer. 110 (10): 2560–2580. doi:10.1038/bjc.2014.162. PMC 4021514. PMID 24691423.


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