VANCOUVER, BC--Use of subcutaneous interleukin-2 (IL-2) to support CD8+ cell maturation in HIV- infected patients appears to be feasible, researchers reported at the 11th International Conference on AIDS.
VANCOUVER, BC--Use of subcutaneous interleukin-2 (IL-2) to supportCD8+ cell maturation in HIV- infected patients appears to be feasible,researchers reported at the 11th International Conference on AIDS.
Nonfunctional CD8+ T cells that are stuck in the G1 phase of thecell cycle pile up in the peripheral blood of HIV-infected individuals.Administration of IL-2 might be able to help these cells overthe G1/S "hump" and enable them to mature into propereffector cells, Richard Lempicki, PhD, said at the meeting.
Dr. Lempicki and his colleagues at the NIH isolated CD8+ cellsfrom the peripheral blood of infected and uninfected donors. Cellswere then separated into CD8+DR+ and CD8+DR- fractions, whichwere cultured with IL-2 and phytohemagglutinin (PHA). The culturedcells were examined for proliferative response, viability, cellcycle stage, and apoptosis.
The results showed that patients with HIV infection had an increasedproportion of cells blocked at the G1/S phase of the cell cycleand that these cells were undergoing an elevated rate of apoptosisin vitro.
The addition of IL-2 resulted in high proliferative responses,suggesting that "in addition to inducing expansion of CD4+cells, IL-2 immunotherapy may also induce CD8+ T cells to continuethrough the cell cycle normally," Dr. Lempicki said.
Tests of subcutaneous IL-2 therapy in the clinic look promising.This is significant because of the expense and inconvenience ofintravenous dosing. Subcutaneous doses can be self-administeredat home.
Richard Davey, MD, of the NIH, reported that subcutaneous IL-2produced "dramatic increases in CD4 count and CD4 percentage"in patients with early HIV (baseline CD4 counts greater than 500cells/mm³).
"The combination of antiretroviral medications and intermittenttherapy with subcutaneous IL-2 has the potential to halt the naturalprogression of HIV infection by maintaining CD4 counts in thenormal range for an extended period," Dr. Davey said.