The modulation of immune function by a-L-fucose
Carbohydrate moieties serve as important antigenic and receptor sites for many lymphocyte activities. The addition of exogeneous monosaccharides and their effects on various leukocyte fonctions has provided useful probes for the study of cell-cell interaction. In this report we studied the potential role of a-L-fucose in the cellular interactions involved in mitogen-, antigen- and alloantigen-induced proliferation and the activation of nonspecific cytolytic cells. Different monosaccharides were tested for their activity when added to uni- and bidirectional mixed lymphocyte reaction [MLC] as well as to mitogen [ConA. PHA, PWM]-stimulated cultures. Only a-L-fucose blocked the MLC reaction in a dose-dependent fashion while having no effect on mitogen stimulation although antigen-specific stimulation was also blocked by fucose. Similarly a-L-fucose specifically inhibited the MLC-induced generation of suppressor cells. The generation and the effector phase of ConA-induced suppressor cells was net affected by fucose, indicating that different receptors are involved than in the generation of antigen- specific suppression. Pretreatment of the MLC responder cells with fucose deshydrogenase abolished the MLC reaction while stimulator cell pretreatment had no effect, suggesting that the recognition site of the responders contained a-L-fucose. In addition, a-fucose, significantly enhanced the cytolytic capacity of MLC-induced or preincubated effector cells. The increase in activity was seen against cytotoxic T lymphocyte [CTL] targets [:relevant PHA blasts], natural killer [NK] cell targets [:K5B2] and natural cytotoxic cell [NC] targets [:MA-160]. In addition, traditionally NK-insensitive targets [Raji cells. irrelevant and autologous PHA blasts] were lysed after preincubation of effector cells is with fucose, although ADCC activity did not increase. NK or CTL activity was not significantly changed by the addition of fucose directly to assay cultures. The proportion of target-binding cells was not affected but the percentage of lytic conjugates was doubled when effector cells were preincubated with fucose. Significant augmentation of NK activity could be observed within 24 hours of incubation with a-L-fucose. Conversely, when fucose was added more than 24 hours after initiation of the culture, the increase in cytolytic activity was not seen. Parallel to the increase in cytolytic activity, following preincubation with a-L-fucose, an increase in the expression of a newly defined human NC cell marker, HNC-1A3 was observed. The populations expressing antigens defined by the antibodies OKT8, Leu7, Leu11 and CKM1 showed no quantitative change. The treatment of cells with OKM1 and complement [C], before culture, ellminated fucose-enhanced killing, whereas simliar treatment with OKT8 or OKT3 and C’ had no significant effect. Enriched OKM1+ cells were capable of responding to fucose. The effector cells of fucose-activated killing were not mainly HNC-1A3+ cells in spite of their significant increase after fucose induction, but the activity was partially sensitive to depletion by OKM1, Leu11, OKT8 antibodies plus C' and only very slightly to OKT3 antibody plus C’. The production of interferon or interleukin 1 was not augmented in fucose-induced cultures whereas there was a slight increase in interleukin 2 production. Fucose activation was not inhibited by the presence of anti IL-2 antibodies or cyclosporin A which suggests that IL-2 does not play a major role in fucose-induction of killing. These results provide evidence that a-L-fucose is capable of augmentingnon-specific cytotoxic activity by an IL-2 independant mechanism. In addition, apparent competitive inhibition by exogenous fucose of cell-cell interaction required for the MLC reaction suggests that this monosaccharide is an essential constituent of allogeneic recognition sites.