Sialoglycolipids shed by
tumor cells have been implicated in
tumor-induced inhibition of T-lymphocyte responses to
interleukin-2 (IL-2). In the present study, we have used
glycophorin A, the major
sialoglycoprotein of the human erythrocyte membrane, to investigate whether shedding of
glycoproteins might also contribute to immunosuppression.
Glycophorin A inhibited IL-2-stimulated proliferation of the IL-2-dependent cell lines HT-2 and CTLL-2 in a dose-dependent manner. Time course studies on synchronized cell populations indicated that the
glycoprotein acted early in the activation process. On the other hand,
glycophorin A had essentially no effect on IL-1-mediated stimulation of the IL-1-sensitive thymocyte cell line EL-4 NOB-1. Gel filtration FPLC demonstrated that
IL-2 was able to bind to
glycophorin aggregates under physiological conditions. Reconstituted vesicles containing
glycophorin were also shown to bind
IL-2. In addition, both soluble
glycophorin aggregates and
lipid vesicles containing
glycophorin blocked binding of
IL-2 to high-affinity cellular
IL-2 receptors. Taken together, these results suggest that shedding of
tumor sialoglycoproteins with
oligosaccharide chains similar to
glycophorin A might contribute to negative modulation of IL-2-mediated immune responses.