Interleukin-2 up-regulates expression of the human immunodeficiency virus fusion coreceptor CCR5 by CD4(+) lymphocytes in vivo

Intermittent interleukin-2 (IL-2) therapy can substantially increase CD4(+) T cell counts of human immunodeficiency virus (HIV)-infected subjects. Adm inistration of IL-2 led to transient up-regulation of CCR5 on CD4(+) T cell s; up to 87% of CD4(+) cells expressed CCR5 after a 5-day cycle, with retur n to baseline levels within 2 weeks. Unlike in vitro studies, CCR5 was coex pressed with CD45RA and CXCR4 on CD4(+) T cells after IL-2 therapy. The obs erved increase in coreceptor expression was nor associated with detectable increases in viral replication. IL-2 therapy induced CCR5 expression in >90 % of circulating memory CD4(+) T cells, determined to be a long-term reserv oir of HIV, suggesting significant activation of these cells. These studies demonstrate that levels of expression of HIV coreceptors alone do not alwa ys 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 im mune system.