CD8 T-cells play a crucial role in controlling HIV replication during the early phase of infection. HIV-specific CD8 T-cells are targeted at the dominant viral variant and their emergence is associated with a rapid fall in viral load before the development of an antibody response.
A majority of the CD8 T-cells generated during primary infection die within a few weeks, leaving a reservoir of HIV-specific CD8 memory T-cells that will persist, regardless of the presence of antigen or CD4 helper T-cells. Researchers have found that viral load is better controlled in people whose HIV-specific CD8 T-cells mature fully into 'effector memory' T-cells.1 2
Several theories have attempted to account for the gradual failure of CD8 T-cells to control HIV replication. The 'viral escape' theory states that the cells begin to lose the ability to recognise HIV's genetic sequences due to the high level of viral turnover and mutation. One study found that CD8 T-cells lose their ability to recognise and kill viral variants, even though they may be responsive to normal 'wild type' viruses.
Researchers compared CD8 cytotoxic T-cells from HIV-infected asymptomatic individuals with those from symptomatic AIDS patients and found that CD8 T-cells from asymptomatic individuals could recognise and kill both types of target cells. In contrast, the CD8 T-cells from symptomatic patients, while still able to recognise and eliminate the laboratory strain targets, no longer killed target cells infected with their own virus. Additionally, HIV-specific CD8 T-cells may fail to produce the cytotoxic molecule, perforin, which CD8 cells use to kill virus-infected cells.3
Without helper T-cells, which slowly disappear during HIV disease, the CD8 T-cells are unable to keep up with the increasingly diverse population of HIV inside the body. As HIV mutates in the body, due to several factors including pressure from antiretroviral medications, these CD8 T-cells become increasingly irrelevant.
CD8 T-cells have been shown to express CD4 receptors on their surface following activation through the T-cell receptor, permitting infection by HIV. Some suggest this is a mechanism through which CD8 T-cells become depleted late in infection.
A recent study suggests that in chronic HIV-1 infection, the constant presence and pressure of HIV-1 antigen causes the functional impairment of virus-specific CD8 T-cell response. As antiretroviral treatment was able to reverse this impairment by reducing the amount of antigen, it suggests that the amount of antigen is the cause and not the result of CD8 T-cell depletion.4
HIV-specific CD8 T-cells that proliferate and produce IL-2 are associated with HIV-specific CD4 T-cells with the same proliferative and IL-2 secreting characteristics. This is usually only seen in people who can control viral load, such as long-term non-progressors.5 6 Strong CD4 T-helper cell and CD8 T-cell responses correlate with long-term non-progression. A therapeutic vaccine that would restore HIV-specific CD4 T-cell and CD8 T-cell responses is one approach that has been looked at to help immune control of HIV.
High levels of the activation marker human leukocyte antigen (HLA)-DR on CD8 T-cells has been associated with slower disease progression, as has decreased antigen expression of CD38 on CD8 cells.7 8 9 10 Very rarely, an efficient CD8 T-cell response can occur before HIV has started to replicate in CD4 T-cells or macrophages. This can prevent HIV infection before the production of HIV antibodies. This may occur more frequently in newborn babies than in adults.