CD4+/CD8+ ratio

The CD4⁺/CD8⁺ ratio is the ratio of T helper cells or regulatory T cells (T_regs) (with the surface marker CD4) to cytotoxic T cells (with the surface marker CD8). Both CD4⁺ and CD8⁺ T cells contain several subsets.

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. An inverted CD4⁺/CD8⁺ ratio (namely, less than 1/1) indicates an impaired immune system. Conversely, an increased CD4⁺/CD8⁺ ratio corresponds to increased immune function.

Obesity and dysregulated lipid metabolism in the liver leads to loss of CD4⁺, but not CD8⁺ cells, contributing to the induction of liver cancer. Regulatory T cells (T_regs) decline with expanding visceral fat, whereas CD8⁺ T-cells increase.

Decreased ratio with infection

A reduced CD4⁺/CD8⁺ ratio is associated with reduced resistance to infection.

Patients with tuberculosis show a reduced CD4⁺/CD8⁺ ratio.

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. 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. Declining CD4⁺/CD8⁺ ratio has been found to be a prognostic marker of HIV disease progression.

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. 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.

Decreased ratio with aging

A declining CD4⁺/CD8⁺ ratio is associated with ageing, and is an indicator of immunosenescence. 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. 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. Antibodies against CD8⁺ T-cells reduces inflammation associated with diet-induced obesity, indicating that CD8⁺ T-cells are an important cause of the inflammation. CD8⁺ cell recruitment of macrophages into adipose tissue can initiate a vicious cycle of further recruitment of both cell types.

Elderly persons commonly have a CD4⁺/CD8⁺ ratio less than 1:1. One study reported that 8.0% of people aged 20-29 years and 15.6% of people aged 60-90 years have a CD4⁺/CD8⁺ ratio less than 1:1.

Obesity is associated with a reduced CD4⁺/CD8⁺ ratio, and obesity tends to increase with age. A study of Swedish elderly found that a CD4+/CD8+ ratio less than one was associated with short-term likelihood of death.

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

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. 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.

See also

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

References