Cloned T-cell proliferation and synthesis of specific proteins are inhibited by quinine

Abstract

Recombinant human interleukin 2 (rIL-2) drives the proliferation of the cloned murine T-helper line L2. The initial G1 activation occurs during the first 20 hr after stimulation, with DNA synthesis (S phase) beginning approximately 20 hr after rIL-2 stimulation. Three patterns of protein synthesis were observed during G1 activation. Type I proteins (e.g., p72 and p66) were synthesized at near maximal rates as early as 4 hr after stimulation, with little change in rates of synthesis through the G1 to S phase transition. Type II proteins (e.g., p52 and p36) were detectable early after stimulation, but their rates of synthesis continued to increase throughout G1 activation, becoming maximal 24-28 hr after stimulation. Type III proteins (e.g., p93, p89, and p63) were synthesized maximally 4 or 8 hr after rIL-2 stimulation, then their rates of synthesis declined markedly to prestimulation levels. Type II proteins, p52 and p36, were shown to be correlated with cell proliferation, since their rates of synthesis were maximal while L2 cells were proliferating and declined as the cells returned to a quiescent state. The potassium channel blocker quinine inhibited cell growth and the synthesis of p52 and p36 when added 0 or 2 hr after rIL-2 stimulation but not when added 6 hr after rIL-2 stimulation. Thus, a quinine-sensitive event occurring in L2 cells between 2 and 6 hr after rIL-2 stimulation is necessary for synthesis of type II proteins, DNA synthesis, and cell proliferation.