T cells are a type of white blood cell that is central to your immune defense. There are four types which serve different functions:
- CD8 T cells are considered "killers" because their function is to destroy any cells in the body that harbor a virus, bacteria, or other disease-causing agents (pathogens).
- CD4 T cells are considered "helpers" because they start up the immune response.
- Suppressor T cells are responsible for turning off the immune response when a threat has been neutralized.
- Memory T cells remain on guard once a threat has been neutralized and "sound off the alarm" if the threat ever returns.
The CD4/CD8 ratio is one of the blood tests used to monitor your immune system if you have human immunodeficiency virus (HIV). It compares the proportion of so-called "helper" CD4 T cells to "killer" CD8 T cells, the value of which can help predict the likely course of the disease.
This article will guide you through how CD4 and CD8 cells interact, what the CD4/CD8 ratio tells us, some conditions in which the ratio can be either high or low, and how often you may need to be tested to monitor an illness.
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How CD4 and CD8 T Cells Interact
CD4 and CD8 are simply two different types of glycoprotein found on the surface of T cells and other lymphocytes (the class of white blood cells central to the immune system).
CD4 T cells work by triggering an immune response when faced with a pathogen. CD8 T cells respond by attacking the tagged pathogen and neutralizing it. Suppressor T cells then "turn off" CD4 activity when a sufficient immune response has been achieved.
What is a normal CD4/CD8 ratio?
A CD4/CD8 ratio is considered normal when the value is between 1.0 and 4.0. In a healthy individual, that translates to roughly 30%–60% CD4 T cells in relationship to 10%–30% CD8 T cells.
When a person is first infected with HIV, there is generally a 30% drop in the number of CD4 T cells as HIV targets these cells and depletes their numbers. By contrast, CD8 T cells will generally increase by about 40%, although their ability to neutralize the virus will wane over time as there are simply fewer CD4 T cells to trigger an effective response. The CD4/CD8 ratio tends to decrease as we age, making people more susceptible to pathogens.
When HIV therapy is initiated promptly, the ratio will generally return to normal. However, if the treatment is delayed until the immune system is seriously damaged, the body's ability to create new CD4 T cells will weaken. If this happens, the ratio may never rise much above 1.0.
What the CD4/CD8 Ratio Tells Us
The prognostic (predictive) value of CD4/CD8 is considered less relevant to the management of HIV than it was 20 years ago. Back then, there were fewer, less effective drugs available to treat HIV. While the value can still help us determine the age of the infection and yourrisk of mortality, changes have been made in recent years.
There is now greater emphasis placed on sustaining viral control (as measured by anundetectable viral load).Doing so helps slow disease progression and avoids the development ofdrug resistance.
With that being said, increasing focus has been placed on the use of the CD4/CD8 ratio in people with long-term HIV infection, Recent studies have suggested that people with a low CD4/CD8 ratio who have been on treatment for years are at an increased risk of non-HIV-related illness and death.
There are several other areas in which the CD4/CD8 ratio may also be important. In epidemiological research, the ratio can be used to measure virulence (the ability to cause disease) of HIV in different populations or over specific periods.
It can also be used to predict the likelihood of immune reconstitution inflammatory syndrome (IRIS), a serious reaction that can sometimes occur when a person starts HIV therapy. If the baseline CD4 count is low and is accompanied by a CD4/CD8 ratio below 0.20, the risk of IRIS increases significantly.
Similarly, research has shown that a low CD4/CD8 count in babies born to HIV-positive mothers can be used to predict whether that baby will seroconvert (become HIV-positive too). The likelihood of this increases dramatically when the ratio falls below 1.0. This is especially relevant in developing countries where the rate of mother-to-child transmissions has dropped but the number of postnatal seroconversions remains high.
The CD4/CD8 ratio test is most frequently used to monitor HIV status. However, it can also be used to diagnose and assess other conditions.
Which Health Conditions Have a Low CD4/CD8 Ratio?
Aside from in HIV/AIDS, the CD4/CD8 ratio can be low in conditions including:
- Infectious mononucleosis
- Bone marrow problems related to chemotherapy
- Anemia
- Chronic lymphocytic leukemia
- Hodgkin disease (lymphoma)
- Multiple sclerosis, myasthenia gravis, or another nervous system condition
- DiGeorge syndrome
- Organ transplantation
Which Health Conditions Have a High CD4/CD8 Ratio?
The CD4/CD8 ratio can be high in conditions including:
- Major infection
- Viral infection
- Type of blood cancer
How Often to Get Tested
For people newly diagnosed with HIV, routine blood monitoring should be performed at the time of entry into care and then every three to six months afterward. This includes the CD4 count and viral load. Once you have been on treatment and have maintained an undetectable viral load for a least two years:
- CD4 monitoring can be performed every 12 months for people whose CD4 count is between 300 and 500.
- CD4 monitoring may be considered optional for those with CD4 counts over 500.
Summary
The CD4/CD8 ratio is a blood test used to monitor the immune systems of people with HIV and other disorders. CD4 and CD8 cells react correspondingly to each other and their ratio (whether low or high) can indicate certain illnesses like HIV, multiple sclerosis, or blood cancer. CD4/CD8 ratio testing is typically done regularly, from the first sign of an illness, to monitor immune response.
7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Okoye AA, Picker LJ. CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure. Immunol Rev. 2013;254(1):54-64. doi:10.1111/imr.12066
Eisinger RW, Dieffenbach CW, Fauci AS. HIV Viral Load and Transmissibility of HIV Infection: Undetectable Equals Untransmittable. JAMA. 2019;321(5):451-452.doi:10.1001/jama.2018.21167
Seng R, Goujard C, Krastinova E, et al. Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ cell count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy. AIDS. 2015;29(5):595-607. doi:10.1097/QAD.0000000000000571
Li CX, Li YY, He LP, et al. The predictive role of CD4+ cell count and CD4/CD8 ratio in immune reconstitution outcome among HIV/AIDS patients receiving antiretroviral therapy: an eight-year observation in China. BMC Immunol. 2019;20(1):31. Published 2019 Aug 28. doi:10.1186/s12865-019-0311-2
Clinicalinfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection.
MedlinePlus. CD4 Lymphocyte Count.
OSF Healthcare. Tests & Procedures - CD4-CD8 Ratio.
Additional Reading
Mahnke, Y.; Greenwald, J.; DerSimonian, R.; et al. Selective expansion of polyfunctional pathogen-specific CD4 T cells in HIV-1–infected patients with immune reconstitution inflammatory syndrome. Blood. 2012; 119(13):3105-3112. DOI: 10.1182/blood-2011-09-380840.
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Dr. Sifris is an HIV specialist and Medical Director of LifeSense Disease Management. Myhre is a journalist and HIV educator.
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