The Role of CD4 T-Cells in an HIV Infection

Immune Cells Are the Primary Targets for HIV

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Healthy CD4+ T-cell. Photo credit: National Institute of Allergy and Infectious Diseases (NIAID)

T-cells are a subset of white blood cells that play an important role in the body's immune system. CD4 is, by contrast, a type of glycoprotein found on the certain immune cells like T-cells, macrophages, and monocytes.

CD4 T-cells are considered "helper" cells because they do not neutralize infections but rather triggers the body's response to infections. In response, CD8 T-cells—classified as such because of the type of glycoprotein on their surface—play a part as so-called "killer" cells by producing antiviral substances (antibodies) that help fight off foreign invaders.

The Role CD4 T-Cells in and HIV Infection

One of the conundrums of HIV infection is that the very cells meant to initiate an immune defense are the same ones targeted for infection by HIV. As a retrovirus, HIV needs to infect certain "host" cells in order to make copies of itself. CD4 cells are the prime targets for this in the course of an infection.

During infection, HIV attaches to these helper cells, emptying its genetic material within so that the host's genetic coding can be altered to produce other HIV virions. In doing so, the host CD4 cell is killed, and its ability to trigger an immune defense is to gradually deplete to such a point as to leave the body open to opportunistic infections.

The dynamics of an HIV are such that "killer" CD8 T-cells are increasingly left blind in an advancing infection and eventually become unable to cope with the growing population of HIV (as measured by the viral load).

If left untreated, the immune system will, in all but rare cases, completely collapse (or become compromised).

How Do We Measure CD4 T-Cells (and Why)?

By determining how many functioning CD4 cells are circulating in the blood, a doctor can determine the status of a person's immune system. A simple blood tested called the CD4 count estimates the number of  functioning CD4 cells in a cubic millimeter of blood.

The higher the CD4 count, the stronger the immune function.

 In a healthy adult, a normal CD4 count can vary enormously (by population, age group, etc.)  but is typically around 500 to 1500 cells per cubic millimeter of blood (mL). When it falls below 200, however, then the disease is classified as AIDS (acquired immune deficiency syndrome). It is during this time that the most serious opportunistic infections are known to occur as the immune systems is effectively compromised by infection.

Prior to 2016, CD4 counts had used as means by which to determine when to start antiretroviral therapy (ART). But in recent years that role has been changed as global authorities now endorse the immediate initiation of HIV therapy on diagnosis (rather than waiting until the CD4 count dropped below 500 cells/mL, as was the previous guideline).

The CD4 count is also used to monitor an individual's response to therapy, with earlier initiation of ART generally correlating to more robust immune reconstitution.

By contrast, people starting ART at very low CD4 counts (under 100 cells/mL) often have a more difficult time reconstituting their CD4 counts to normal levels, particularly after a severe bout of illness.

It is, therefore, important to get tested as per the current U.S. guidelines and seek immediate care in the event of an HIV-positive diagnosis. If treatment is started promptly, people living with HIV now have a far better chance of living normal and healthy lifespans.

Sources:

National Institutes of Health (NIH). "Starting antiretroviral therapy early improves outcomes for HIV-infected individuals." Bethesda, Maryland; issued May 27, 2015.

Seng, R.; Goujard, C.; Krastinova, E.; et al. "Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy."AIDS. January 13, 2015; published ahead of print; DOI: 10.1097/QAD.0000000000000571.

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