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.
Nonfunctional CD8+ T cells that are stuck in the G1 phase of the cell cycle pile up in the peripheral blood of HIV-infected individuals. Administration of IL-2 might be able to help these cells over the G1/S "hump" and enable them to mature into proper effector cells, Richard Lempicki, PhD, said at the meeting.
Dr. Lempicki and his colleagues at the NIH isolated CD8+ cells from the peripheral blood of infected and uninfected donors. Cells were then separated into CD8+DR+ and CD8+DR- fractions, which were cultured with IL-2 and phytohemagglutinin (PHA). The cultured cells were examined for proliferative response, viability, cell cycle stage, and apoptosis.
The results showed that patients with HIV infection had an increased proportion of cells blocked at the G1/S phase of the cell cycle and that these cells were undergoing an elevated rate of apoptosis in 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 continue through 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 of intravenous dosing. Subcutaneous doses can be self-administered at home.
Richard Davey, MD, of the NIH, reported that subcutaneous IL-2 produced "dramatic increases in CD4 count and CD4 percentage" in patients with early HIV (baseline CD4 counts greater than 500 cells/mm³).