Murine leukemia. Proposed role for gangliosides in immune suppression

Abstract

Glycolipid-bound sialic acid levels were elevated 2 to 4-fold in the sera of two strains of mice bearing thymic lymphoma produced either spontaneously (AKR/J) or due to chemical carcinogenesis [Swiss mice injected with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboximide]. The serum glycolipid-bound sialic acid level reflected the tumor burden of the AKR/J mice during the early stages of leukemogenesis. Furthermore, the elevation was found to coincide with the ontogenesis of thymic lymphoma and not to be simply an age-dependent phenomenon. TLC analysis of Florisil column-purified gangliosides from the sera of AKR/J and Swiss mice suggested presence of gangliosides with mobilities very close to GM2 and GM3 standards respectively. On the premise that the elevated glycolipid levels in circulation might interfere with normal lymphocyte functions, the immunoinhibitory properties of exogenously added mixed gangliosides were examined on tests of in vitro correlates of the immune response. Gangliosides inhibited concanavalin A and lipopolysaccharide-induced [ 3 H]-thymidine, [ 14 C]-leucine and [ 3 H]-lysine uptake by normal AKR/J mouse thymocytes and spleen cells. Mixed gangliosides also suppressed the two-way mixed lymphocyte reaction of AKR/J × Swiss and AKR/J × DBA/2 spleen cells. These and other results strongly suggest a general immunologically relevant role for gangliosides in the ontogeny of thymic lymphoma of mice.