Apoptosis and AIDS

The hallmark of AIDS (acquired immunodeficiency syndrome) is the decline in the number of the patient's CD4⁺ T cells (normally about 1000 per microliter (µl) of blood). CD4⁺ T cells are responsible, directly or indirectly (as helper cells), for all immune responses. When their number declines below about 200 per µl, the patient is no longer able to mount effective immune responses and begins to suffer a series of dangerous infections.

What causes the disappearance of CD4⁺ T cells?

HIV (human immunodeficiency virus) invades CD4⁺ T cells, and one might assume that it this infection by HIV that causes the great dying-off of these cells. However, that appears not to the main culprit. Fewer than 1 in 100,000 CD4⁺ T cells in the blood of AIDS patients are actually infected with the virus.

So what kills so many uninfected CD4⁺ cells?

The answer is clear: apoptosis.

The mechanism is not clear. There are several possibilities. One of them:

• All T cells, both infected and uninfected, express Fas.
• Expression of a HIV gene (called Nef) in a HIV-infected cell causes
  • the cell to express high levels of FasL at its surface
  • while preventing an interaction with its own Fas from causing it to self-destruct.
• However, when the infected T cell encounters an uninfected one (e.g. in a lymph node), the interaction of FasL with Fas on the uninfected cell kills it by apoptosis.