# 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.
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 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 (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 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 (T$_h$1 and T$_h$2) and regulatory T cells (T$_{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.