Soluble inhibitory factors (SIF) have been demonstrated in the sera of
cancer patients, which interfere with the T-cell activation process. We have shown that the major contributory factor to the inhibitory effect of sera from patients with
Hodgkin's disease (HD) could be the soluble form of
Interleukin-2 receptors (sIL-2R). The parameters studied to show the presence of SIF include (i) inhibiton of
mitogen-induced proliferation; (ii) status of high- and low-affinity IL-2R; and (iii) internalization of IL-2-IL-2R complex, by lymphocytes from healthy donors activated with
mitogen in presence of HD sera. Parameters studied to show the inhibitory role of sIL2R include (i) quantitation of sIL-2R in HD sera; (ii) effect of high-sIL-2R-containing sera on
mitogen-induced proliferation and detection of
IL-2 in activated lymphocyte culture supernatants; (iii) effect of exogenous
IL-2 supplementation; and (iv) abrogation of inhibitory activity of sIL-2R-containing sera after passing them through
IL-2 affinity columns. Our results show that 6/23 HD sera tested had high inhibitory activity (greater than 50% inhibition of
mitogen-induced proliferation). The SIF did not affect expression of high- and low-affinity
IL-2 receptors, or internalization of the complex by activated lymphocytes. Ten of the 15 sera tested showed significantly high levels of sIL-2R. Pooled sera with high sIL-2R content inhibited
mitogen-induced proliferation of normal lymphocytes with a concomitant reduction in
IL-2 activity in the lymphocyte culture supernatants. When supplemented with exogenous
IL-2, there was a partial recovery of the inhibitory effect. When sIL-2R containing serum pool was passed on
IL-2 affinity columns, the inhibitory effect was reduced. The eluted "sIL-2R" adsorbed on the
IL-2 column showed anti-proliferative effect.