ENGAGEMENT OF THE CD4 RECEPTOR INHIBITS THE INTERLEUKIN-2-DEPENDENT PROLIFERATION OF HUMAN T-CELLS TRANSFORMED BY HERPESVIRUS-SAIMIRI

Infection with Herpesvirus Saimiri, a tumor virus of non-human primate s, transformed human CD4(+) T cell clones to permanent interleukin (IL )-2-dependent growth without need for restimulation with antigen and a ccessory cells. The IL-2-dependent proliferation of these cells was dr amatically inhibited by soluble anti-CD4 whole antibodies, F(ab')(2) a nd Fab fragments, and also by gp 120 of human immunodeficiency virus. The inhibition was not due to cell death and could be overcome by high concentrations of exogenous IL-2. Cell surface expression of CD4, and to a lesser degree the density of the IL-2 receptor alpha chain, were reduced upon anti-CD4 treatment. After long lasting (>12h) incubation with anti-CD4, abundance and activity of CD4-bound p56(lck) were dimi nished while the free fraction of p56(lck) remained unchanged. Since I L-2 binding to its receptor activated only the CD4-bound fraction of p 56(lck), the IL-2-induced p56(lck) activity was diminished after long- term CD4 ligation. Taken together, our results suggest a cross talk be tween CD4- and IL-2 receptor-mediated signaling via p56(lck).