title: 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 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.
authors.affiliation: Immunology Division, Cancer Research Institute, Bombay, India.
authors.forename: R N
authors.initials: RN
authors.lastname: Damle
authors.forename: S H
authors.initials: SH
authors.lastname: Advani
authors.forename: S G
authors.initials: SG
authors.lastname: Gangal
mesh_terms: D001682:Biological Availability; D002846:Chromatography, Affinity; D006131:Growth Inhibitors / Q000097:blood* / Q000494:pharmacology; D006689:Hodgkin Disease / Q000097:blood*; D006801:Humans; D007376:Interleukin-2 / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008934:Mitogens / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
chemical_list: D006131:Growth Inhibitors; D007376:Interleukin-2; D008934:Mitogens; D015375:Receptors, Interleukin-2