Cell transfer techniques use immune cells taken from an individual which are treated in the laboratory to clone millions of copies. The clones are then re-infused in the hope that they will improve immune responses and provide a springboard for the generation of many copies in the body. These techniques have been used to control Epstein-Barr virus and cytomegalovirus after bone marrow transplants.

Unfortunately, experiments with these approaches have proved disappointing so far. Researchers at the University of Washington in Seattle cloned HIV-specific CD8 T-cells created in the laboratory and infused them into five patients. Three infusions were given to each individual. The infusions were associated with modest antiviral effects at the time of the infusion, but viral load rebounded to baseline within a week of each infusion. However, biopsies revealed an increased level of CD8 T-cells in the lymph nodes after the third infusion, and it was determined that these CD8 T-cells were the ones which had been infused. Longer term follow-up is awaited.

However, another experiment conducted by researchers in Oxford has failed to demonstrate any benefit from infusing CD8 T-cells. The cells died within hours of infusion (Tan 1999).

Some researchers now believe that a poor immune response is not due to low numbers of HIV-specific CD8 T-cells but, rather, due to a lack of activity. This may explain the disappointing results in response to infusions of HIV-specific CD8 T-cells (Lieberman 1999).

Role of the thymus

The thymus is the organ which produces T-cells. Until recently, scientists thought that the thymus stopped producing new T-cells during puberty. In fact, the thymus maintains its ability to produce T-cells throughout a person's life, although its size in adults is much reduced.

A recent study found considerable evidence that ageing does not lead to gaps in the T-cell receptor repertoire of the thymus (Jamieson 1999). Consequently, scientists are now looking to develop ways of increasing the functional capacity of the adult thymus in people successfully treated with antiretroviral therapy, such as with the use of interleukin-7. Such an approach may speed the process of immune reconstitution.

References

Brodie S et al. In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nat Med 5: 34-41, 1999.

Jamieson BD et al. Generation of functional thymocytes in the human adult. Immunity 10: 569-575, 1999.

Lieberman J. Immunotherapy with HIV specific cytotoxic T-lymphocytes. Second Meeting of RIGHT, Washington, 1999.

Tan R et al. Rapid death of adoptively transferred T-cells in acquired immunodeficiency syndrome. Blood 93: 1506-1510, 1999.