Reversal of infectious mononucleosis-associated suppressor T cell activity by D-mannose.

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Abstract
Epstein-Barr virus-induced infectious mononucleosis (IM) is associated with the activation of suppressor T lymphocytes that profoundly inhibit Ig production in vitro. The nature of signals operating in the interaction between IM suppressor T cells and their targets was studied and the possibility that a lectin-like receptor molecule and its specific sugar might provide specificity to this interaction was explored. When D-mannose or some of its derivatives, including a-methyl-D-mannoside, mannose-6-phosphate and mannan, were added to suppressed cultures containing IM T lymphocytes and pokeweed mitogen (PWM)-stimulated normal mononuclear cells, a significant enhancement of Ig production was observed. These sugars had little or no effect on Ig production by the PWM-stimulated responder cells alone and thus the enhanced Ig production could be attributed to the reversal of suppression in the co-cultures by these sugars. This was further confirmed by the observation that the sugars were effective only if present during the first 24 h of culture, a time when IM suppressor T cells exert their principal effect. The effect of sugars on Ig production by suppressed cultures was similar to that achieved by decreasing by .apprx. 4-fold the number of IM T cells in culture. The effect of the sugars is unlikely to represent a form of nonspecific toxicity, since inhibited cultures become responders in the presence of the sugar. Toxicity restricted to the suppressor T cells is unlikely, since preincubation of the T cells with the sugars did not reduce their subsequent ability to suppress in secondary indicator cultures. There was no correlation between the effect of the sugars on T cell proliferation and their effect on T cell-mediated suppression. The reversal of suppression by sugars was dose dependent and demonstrated stereospecificity in that L-mannose was without effect while D-mannose reversed suppression. Evidently, D-mannose and some of its derivatives consistently reverse suppression of Ig production by IM T cells and strongly suggest a role for saccharides as critical components in the cellular receptors involved in certain physiologic immune cell interactions.