Induction of suppressor T cells by neuraminic acid derivatives.

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Abstract
We investigated the effects of α- and β-methylglycosides of N-acetylneuraminic acid and its disaccharide derivatives on the proliferation and immunological functions of murine lymphocytes. The Con A-induced increase of deoxyribonucleic acid (DNA) synthesis was enhanced by some of these neuraminic acid derivatives when they were added to a culture of murine spleen lymphocytes, and the disaccharide nucleosides, 5-fluoro-2', 3'-isopropylidene-5'-O-(4-N-acetyl-2, 4-dideoxy-3, 6, 7, 8-tetra-O-acetyl-1-methoxycarbonyl-D-glycero-α-D-galactooctapyranosyl) uridine (compound 9) and 2', 3'-di-O-acetyl-4-N-acetyl-2, 4-dideoxy-3, 6, 7, 8-tetra-O-acetyl-1-methoxycarbonyl-D-glycero-α-D-galactooctapyranosyl) inosine (compound 10), were especially effective. The above disaccharide nucleosides and their starting materials, 5-fluoro-2', 3'-isopropylidene uridine (FIU) and 2', 3'-di-O-acetylinosine (DAI), suppressed in vitro primary antibody response toward sheep red blood cells (SRBC). In vivo antibody response toward SRBC was also suppressed when compound 9 or 10 was injected intraperitoneally into mice with SRBC. Moreover, lymphocytes incubated with compound 9 or 10 showed suppressor activity on primary anti-SRBC antibody response in vitro. On the other hand, FIU and DAI did not induce the suppressor activity of murine lymphocytes in vivo or in vitro. The induction of suppressor cells by compounds 9 and 10 was abolished by pretreatment of the lymphocytes with anti Thy-1 antiserum plus complement. These results suggest that these disaccharide nucleosides can induce suppressor T cells.

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