American Foundation for AIDS ResearchImportant note: Information in this article was accurate in May 2000. The state of the art may have changed since the publication date.
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CD8+ cell infusions

TreatmentUpdate 107 - 2000 May; Volume 12 Issue 3
Hosein SR Click here for french language version of article

Several studies have found that infusing CD8+ cells into PHAs is generally safe. Results also show that the cells transferred during this process sometimes have anti-HIV activity. Unfortunately the transferred cells do not live long. In one study, about 90% of CD8+ cells died 48 hours after being infused. Researchers are conducting experiments to find out why this happens and to develop ways to extend the life of these CD8+ cells.

According to their latest series of experiments, researchers in Seattle reported infusing about one billion anti-HIV CD8+ cells into HIV-positive subjects. The cells quickly moved to the lymph nodes, which containing large amounts of HIV. Once there, the cells released anti-HIV chemicals.

In previous experiments, researchers found that infusions of anti-HIV CD8+ cells resulted in a temporary reduction of CD4+ cell levels. It is likely that the lost CD4+ cells had been infected with HIV and were killed by the CD8+ cells. As before, the infused CD8+ cells rapidly disappeared from the blood. Within two to three weeks of the infusion, most of the CD8+ cells could no longer be detected.

Trying to keep the cells alive

Future experiments will attempt to keep the infused cells alive for longer periods of time. One method may be to infuse both CD4+ and CD8+ cells together in the hope that, somehow, interaction between the two types of cells will help CD8+ cells live longer. Another research team thinks that infusing CD8+ cells together with another group of cells called dendritic cells may be a useful option.

According to some researchers, bathing CD8+ cells with the immune booster IL-2 (interleukin-2) prior to infusion may prolong their life. Other research suggests that treating CD8+ cells with the immune booster IL-12 (interleukin-12) before infusions may also help prolong their life but this needs to be confirmed.

Whatever the method, researchers are busy searching for a way to keep CD8+ alive or to identify HIV-fighting chemicals they produce so that therapies can one day be developed for PHAs.

REFERENCES

1. Lieberman J, Skolnik PR, Parkerson R, et al. Safety of, Ex-vivo-expanded Human Immunodeficiency Virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients. Blood 1997;90(6):2196-2206.

2. Brodie SJ. Lewinsohn DA, Patterson BK, et al. In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nature Medicine 1999;5(1):34-41.

3. Brodie SJ, Patterson BK Lewinsohn DA, et al. HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death. Journal of Clinical Investigation 2000;105(10):1407-1417.

4. Picker LJ. Proving HIV-1 immunity: new tools offer new opportunities. Journal of Clinical Investigation 2000;105(10)1333-1334.

5. Tan R, Xu X, Ogg GS, et al. Rapid death of adoptively transferred T cells in Acquired Immunodeficiency Syndrome. Blood 1999;93(5):1506-1510.

6. Spiegel HML, Ogg GS, DeFalcon E, et al. Human Immunodeficiency Virus type-1 and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolong periods in the absence of peripheral CD4+ T cells. Journal of Virology 2000;74(2):1018-1022.

7. Ku CC, Murakami M, Sakamoto A, et al. Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 2000;288:675-678.

8. Rinaldo CR, Huang X-L, Fan Z, et al. Anti-Human Immunodeficiency virus Type 1 (HIV-1) CD8+ T-lymphocyte reactivity during combination antiretroviral therapy in HIV-1-infected patients with advanced immunodeficiency. Journal of Virology 2000;74(9):4127-4138.

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