What Are CD4 T-Cells and Why Are They Important?

Immune cells are the primary target of HIV infection

Artist's depiction of a CD4+ lymphocyte amid red blood cells. Getty Images

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 protein 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 protein on their surface — play a part "killer" cells by producing substances (antibodies) that help fight off viruses and other foreign invaders.

The Role CD4 T-Cells in 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).

Types of CD4 T-Cells

More often than not we tend to think of CD4 T-cells as one type of cell. In fact, it was only in the mid-1980s that scientist began identifying various subsets with different functions.

Some are important in activating so-called macrophage and dendritic cells during initial infection, while others direct immune defenses when faced, individually, with parasitic organisms, bacteria, or viruses.

These include subtypes called T-helper 1, T-helper 2, T-helper 9, T-helper 17, regulatory T-cell, and follicular helper T- cell, each of which secretes different types of substance to help neutralize viruses.

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 test 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 are 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 able to restore a person's immune function. 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 life spans.

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 the 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.

Zhu, J. and Paul, W. "CD4 T cells: fates, functions, and faults." Blood. 2008;112:1557-1569.

Luckheeram, R.; Zhou, R.; Verma, A.; et al. "CD4+ T Cells: Differentiation and Functions." Clinical and Developmental Immunology. 2012: 2012(925135); DOI 10.1155/2012/925135.

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