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

A 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

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

A 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 (T_h1 and T_h2) 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.^[17] 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.^[17]

See also

• Helper/suppressor ratio
• List of distinct cell types in the adult human body

References