CD4 T Cell Survival after Intermittent Interleukin-2 Therapy Is Predictive of an Increase in the CD4 T

Administration of interleukin (IL)–2 to human immunodeficiency virus (HIV)–infected patients leads to signifi-cant increases in CD4 T cell counts. We previously have shown that IL-2 induces increased proliferation and survival of CD4 T cells. Deuterium labeling studies were undertaken to study the relationship between IL-2– induced increases in the CD4 T cell count and the effects of IL-2 on cell proliferation and survival. A strong inverse correlation was noted between the rate of decay of the label in CD4 cells and increases in CD4 cell counts (R 0.67; P<.001). This correlation was not seen with the level of proliferating cells. Although the CD4 cell count at baseline and the number of CD4 cells expressing CD25 were also predictive of increases in the CD4 cell count, the rate of decay remained the most statistically significant predictor in multivariate regression models. Thus, an increase in the survival of CD4 T cells appears to be the critical mechanism leading to sustained increases in the CD4 cell counts of HIV-infected patients receiving intermittent IL-2 therapy. Treatment of HIV-1–infected patients with intermittent cycles of interleukin-2 (IL-2) leads to significant and sustained increases in CD4 T cell counts. This effect has been demonstrated in a number of randomized trials and is a result of a selective increase in the number o