Interleukin-2 Up-Regulates Expression of the Human Immunodeficiency Virus Fusion Coreceptor CCR5 by CD4+ Lymphocytes In Vivo

T cells; up to 87% of CD4 + cells expressed CCR5 after a 5-day cycle, with return to baseline levels within 2 weeks. Unlike in vitro studies, CCR5 was coexpressed with CD45RA and CXCR4 on CD4 + T cells after IL-2 therapy. The observed increase in coreceptor expression was not associated with detectable increases in viral repli- cation. IL-2 therapy induced CCR5 expression in 190% of circulating memory CD4 + T cells, determined to be a long-term reservoir of HIV, suggesting significant activation of these cells. These studies demonstrate that levels of expression of HIV coreceptors alone do not always correlate with HIV replication in vivo and that IL-2 therapy activates a majority of memory T cells in the circulation and likely throughout the immune system. Intermittent interleukin-2 (IL-2) therapy has been shown to lead to substantial increases in CD4 1 T cell populations in patients with human immunodeficiency virus (HIV) infection. This IL-2-induced increase in CD4 1 T cell numbers appears to derive from peripheral expansion of preexisting naive and memory CD4 1 T cells (1). Although IL-2 is a potent stimulator