CD4+/CD8+ ratio

The CD4⁺/CD8⁺ ratio is the ratio of T helper cells to cytotoxic T cells. 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 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 CD4⁺ cells 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 through a number of mechanisms, including killing of infected CD4⁺. Acquired immunodeficiency syndrome (AIDS) is a CD4⁺ T cell count below 200 cells per μL. HIV progresses with declining numbers of CD4⁺ and expanding number of CD8+ 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 one. 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 and regulatory T cells 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.