Two mechanisms of inhibition of human lymphocyte proliferation by soluble yeast mannan polysaccharide.

The literature on chronic mucocutaneous candidiasis contains multiple reports which suggest that loss of cell-mediated immunity in this disease may be related in part to the presence of an inhibitory factor(s) present in patient plasma. One such inhibitory factor has been suggested to be mannan polysaccharide released from the cell wall of the pathogen. The present report describes results of experiments to consider mechanisms by which yeast mannan influences proliferative responses of human lymphocytes. Mannan for these experiments was isolated from Saccharomyces cerevisiae. We observed that mannan-mediated inhibition of proliferative responses to a battery of stimuli (phytohemagglutinin, pokeweed mitogen, and Candida, mumps, streptococcus, cytomegalovirus, and herpes simplex virus antigens) was related in part to an effect of copper associated with the mannan and possibly to the superoxide dismutase activity of the mannan-copper complex. Mannan made deficient in copper by use of a copper-chelating resin appeared to inhibit only lymphoproliferation stimulated by the Candida antigen. These results suggest that inhibitory effects of yeast mannans on lymphoproliferative responses may involve at least two mechanisms, one related to hydrogen peroxide production augmented by mannan-copper complexes and another related to still unknown effects independent of the metal ligand. We propose that our results represent a significant novel observation which may be useful in understanding mechanisms of immunoinhibitory effects of C. albicans mannan.