Analysis of regulation of T-cell responses by soluble inhibitory factors from the sera of patients with Hodgkin's disease

Abstract

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 Interleu-kin-2 receptors (slL-2R). The parameters studied to show the presence of SIF include (i) inhibition 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 slL-2R 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 (>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.