INTERLEUKIN-2 RECEPTOR-BETA AND GAMMA-CHAIN DYSREGULATION DURING THE INHIBITION OF CD4 T-CELL ACTIVATION BY HUMAN IMMUNODEFICIENCY VIRUS-1 GP120

We have observed that CD4 T lymphocytes from human immunodeficiency vi rus (HIV)-infected patients marginally express interleukin-2 receptor (IL-2R)beta and IL-2R gamma chains which are essential for IL-2 signal transduction. To analyze this observation further, we studied the inf luence of gp120 on the cell surface expression of IL-2R beta and IL-2R gamma by purified CD4 lymphocyte in vitro. Cross-linking of the T cel l receptors of these lymphocytes initiates entry into the cell cycle a s measured by CD69 and CD71 cell surface expression and [H-3]thymidine incorporation. It also induces the cell surface expression of IL-2R b eta and IL-2R gamma. We have shown that treatment of the CD4 T lymphoc ytes with HIV-1 gp120 before anti-CD3 stimulation impedes cell cycle p rogression as measured by reduced CD71 expression and inhibition of [H -3]thymidine incorporation, Furthermore, cell surface expression of IL -2R beta and IL-2R gamma subunits, which form the functional intermedi ate-affinity IL-2R, are significantly inhibited. More importantly, add ition of exogenous IL-2 does not restore the proliferation of the CD4 T cells treated with gp120, suggesting that cells are anergic and/or t hat the remaining IL-2R are not functional. This is the first study of IL-2R beta and IL-2R gamma dysrcgulation in the context of HIV infect ion and shows that CD4 is also involved in IL-2R expression.