CD8 T-cells are immune cells which play a key role in the cellular immune response (as opposed to the humoral immune response, which involves antibodies). They are sometimes referred to as cytotoxic T-cells, because they are able to detect and kill cells which have been infected by foreign organisms, including HIV-infected cells in test-tube studies.

Research suggests that CD8 T-cells may be central to the body's initial strong immune response following infection with HIV, which dramatically reduces the amount of virus that can be detected in the blood. Their importance is also indicated by evidence that people with high levels of CD8 T-cells may have a better prognosis than people with lower levels. Tests in chimpanzees have suggested that the reason why these animals do not suffer immune damage when inoculated with HIV may be due to their CD8 lymphocytes' ability to inhibit HIV replication.

CD8 T-cells also seem to have non-cytotoxic activity against HIV - that is HIV replication is stopped without infected cells being killed. It is thought that this non-cytotoxic activity is induced by CD8 antiviral factor (CAF) which is a highly effective inhibitor of HIV replication.

CAF was discovered in 1989 by Dr Jay Levy. He found that CD8 T-cells secrete the substance that he named CAF. In late 1995, other researchers reported that CAF appeared to consist of at least three chemokines, called RANTES, MIP-1alpha and MIP-2beta, although Levy disputes this conclusion.

CAF inhibits HIV replication and is associated with non-progression. Levy has shown that in blood or lymph node samples taken from long-term asymptomatic people, HIV cannot replicate in the presence of CD8 cells. CAF is produced at high levels by the CD8 cells of people who are asymptomatic with strong CD8 responses, but little or no CAF is produced by the CD8 cells of people with symptoms. CD8 cells from uninfected as well as HIV-positive people secrete substances that can inhibit HIV replication.

Autologous CD8 infusion is a treatment in which CD8 cells are isolated from an HIV-infected person and stimulated by natural cell-activating proteins such as interleukin-2 (IL-2). They are then reinfused into the body in the hope that they will exert a stronger anti-HIV effect.

Current use

Autologous CD8 infusion is an unlicensed, experimental treatment. The procedure is being tested in the USA using a device called the CELLector, manufactured by Applied Immune Science (AIS), which isolates CD8 cells in the presence of interleukin-2. A phase II study found that people given IL-2 had CD4 count increases, regardless of whether or not they also received CD8 infusions. Those also given CD8 infusion had increases in their CD8 cell count that persisted for up to three months after the last treatment. No difference in clinical outcome or HIV viral load was seen during the nine month study. Some researchers believe that any benefits will be slight and may in fact be attributable to the interleukin-2 rather than the CD8 cells.

One potential drawback is that any HIV-infected cells which are present during activation are likely to be stimulated to produce increased amounts of HIV. It is also unclear how long the CD8 cells would continue to have beneficial effects once reinfused into the body. It is also possible that the CD8 cells might attack uninfected, healthy CD4 cells which have bound onto the gp120 protein released from HIV-infected cells.

No significant toxicities or adverse effects have been observed except for flu-like symptoms during the interleukin-2 infusion.

Getting it

No studies into autologous CD8 infusion are taking place in Britain and the treatment is not known to be available through other means.

Key research

References

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Buchbinder S et al. Long-term HIV-1 infection without immunological progression. AIDS 8(8):1123-1128, 1994.

Castro BA et al. Suppression of human immunodeficiency virus replication by CD8+ cells from infected and uninfected chimpanzees. Cell Immunol 132(1):246-255, 1991.

Cocchi F et al. Identification of RANTES, MIP-1alpha, and MIP-1beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:1811-1815, 1995.

Deresinski SC et al. Randomized multi center comparison of treatment of HIV infected patients: activated CD8+ cells plus rIL-2 plus antiretroviral (AR) therapy vs IL2 plus AR therapy vs AR therapy alone. Second National Conference on Human Retroviruses and Related Infections, Washington, abstract 206, 1995.

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Klimas NG et al. Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion. AIDS 8:1073-1081, 1994.

Levy JA. HIV: From discovery to uncovering features of pathogenesis and long-term survival. Tenth International Conference on AIDS, Yokohama, presentation TS2, 1994.

Lieberman J et al. Safety of autologous, ex vivo-expanded human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients. Blood 90(6):2196-2206, 1997.

Tsuchie H et al. Suppression of HIV replication in vitro by CD8+ T-cells from HIV-infected and HIV-seronegative individuals. International Journal of Sexually Transmitted Diseases and AIDS 8(5):307-310, 1997.

Walker BD et al. HIV specific cytotoxic T lymphocytes in seropositive individuals. Nature 328:345-348, 1987.

Walker CM et al. Inhibition of human immunodeficiency virus replication in acutely infected CD4+ cells by CD8+ cells involves a noncytotoxic mechanism. Journal of Virology 65(11):5921-5927, 1991.

Walker CM et al. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 234:1563-1566, 1986.