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. 1983 Oct 1;158(4):1048–1060. doi: 10.1084/jem.158.4.1048

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

PMCID: PMC2187377  PMID: 6225821

Abstract

Epstein-Barr virus-induced infectious mononucleosis (IM) is associated with the activation of suppressor T lymphocytes that profoundly inhibit immunoglobulin (Ig) production in vitro. We have examined the nature of signals operating in the interaction between IM suppressor T cells and their targets, and explored the possibility that a lectin-like receptor molecule and its specific sugar might provide specificity to this interaction. When D-mannose or some of its derivatives, including alpha- 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 about fourfold 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. Furthermore, 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. In addition, 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 stereo-specificity in that L-mannose was without effect while D-mannose reversed suppression. These data indicate that 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.

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Selected References

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  1. Ashwell G., Morell A. G. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol Relat Areas Mol Biol. 1974;41(0):99–128. doi: 10.1002/9780470122860.ch3. [DOI] [PubMed] [Google Scholar]
  2. De Waele M., Thielemans C., Van Camp B. K. Characterization of immunoregulatory T cells in EBV-induced infectious mononucleosis by monoclonal antibodies. N Engl J Med. 1981 Feb 19;304(8):460–462. doi: 10.1056/NEJM198102193040804. [DOI] [PubMed] [Google Scholar]
  3. Decker J. M., Elmholt A., Muchmore A. V. Spontaneous cytotoxicity mediated by invertebrate mononuclear cells toward normal and malignant vertebrate targets: inhibition by defined mono- and disaccharides. Cell Immunol. 1981 Mar 15;59(1):161–170. doi: 10.1016/0008-8749(81)90443-3. [DOI] [PubMed] [Google Scholar]
  4. Fleisher T. A., Greene W. C., Blaese R. M., Waldmann T. A. Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. II. Characterization of a soluble suppressor of B cell immunoglobulin production. J Immunol. 1981 Mar;126(3):1192–1197. [PubMed] [Google Scholar]
  5. Fleisher T. A., Greene W. C., Uchiyama T., Goldman C. K., Nelson D. L., Blaese R. M., Waldmann T. A. Characterization of a soluble suppressor of human B cell immunoglobulin biosynthesis produced by a continuous human suppressor T cell line. J Exp Med. 1981 Jul 1;154(1):156–167. doi: 10.1084/jem.154.1.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Forbes J. T., Bretthauer R. K., Oeltmann T. N. Mannose 6-, fructose 1-, and fructose 6-phosphates inhibit human natural cell-mediated cytotoxicity. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5797–5801. doi: 10.1073/pnas.78.9.5797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GELB L. D., LERNER A. M. REOVIRUS HEMAGGLUTINATION: INHIBITION BY N-ACETYL-D-GLUCOSAMINE. Science. 1965 Jan 22;147(3656):404–405. doi: 10.1126/science.147.3656.404. [DOI] [PubMed] [Google Scholar]
  8. Geltosky J. E., Weseman J., Bakke A., Lerner R. A. Identification of a cell surface glycoprotein involved in cell aggregation in D. discoideum. Cell. 1979 Oct;18(2):391–398. doi: 10.1016/0092-8674(79)90058-8. [DOI] [PubMed] [Google Scholar]
  9. Grabel L. B., Rosen S. D., Martin G. R. Teratocarcinoma stem cells have a cell surface carbohydrate-binding component implicated in cell-cell adhesion. Cell. 1979 Jul;17(3):477–484. doi: 10.1016/0092-8674(79)90255-1. [DOI] [PubMed] [Google Scholar]
  10. Greene W. C., Fleisher T. A., Waldmann T. A. Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. I. Characterization of a soluble suppressor T cell proliferation. J Immunol. 1981 Mar;126(3):1185–1191. [PubMed] [Google Scholar]
  11. Haynes B. F., Schooley R. T., Payling-Wright C. R., Grouse J. E., Dolin R., Fauci A. S. Emergence of suppressor cells of immunoglobulin synthesis during acute Epstein-Barr virus-induced infectious mononucleosis. J Immunol. 1979 Nov;123(5):2095–2101. [PubMed] [Google Scholar]
  12. Henle W., Henle G. E., Horwitz C. A. Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Hum Pathol. 1974 Sep;5(5):551–565. doi: 10.1016/s0046-8177(74)80006-7. [DOI] [PubMed] [Google Scholar]
  13. Kobata A., Grollman E. F., Ginsburg V. An enzymatic basis for blood type B in humans. Biochem Biophys Res Commun. 1968 Jul 26;32(2):272–277. doi: 10.1016/0006-291x(68)90380-x. [DOI] [PubMed] [Google Scholar]
  14. Kobata A., Grollman E. F., Ginsburg V. An enzymic basis for blood type A in humans. Arch Biochem Biophys. 1968 Mar 20;124(1):609–612. doi: 10.1016/0003-9861(68)90373-1. [DOI] [PubMed] [Google Scholar]
  15. Koszinowski U. H., Kramer M. Selective inhibition of T suppressor-cell function by a monosaccharide. Nature. 1981 Jan 15;289(5794):181–184. doi: 10.1038/289181a0. [DOI] [PubMed] [Google Scholar]
  16. MacDonald H. R., Cerottini J. C. Inhibition of T cell-mediated cytolysis by 2-deoxy-D-glucose (2-DG): differential effect of 2-DG on effector cells isolated early or late after alloantigenic stimulation in vitro. J Immunol. 1979 Mar;122(3):1067–1072. [PubMed] [Google Scholar]
  17. McKenzie I. F., Clarke A., Parish C. R. Ia antigenic specificities are oligosaccharide in nature: hapten-inhibition studies. J Exp Med. 1977 Apr 1;145(4):1039–1053. doi: 10.1084/jem.145.4.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Muchmore A. V., Decker J. M., Blaese R. M. Evidence that specific oligosaccharides block early events necessary for the expression of antigen-specific proliferation by human lymphocytes. J Immunol. 1980 Sep;125(3):1306–1311. [PubMed] [Google Scholar]
  19. Muramatsu T., Gachelin G., Damonneville M., Delarbre C., Jacob F. Cell surface carbohydrates of embryonal carcinoma cells: polysaccharidic side chains of F9 antigens and of receptors to two lectins, FBP and PNA. Cell. 1979 Sep;18(1):183–191. doi: 10.1016/0092-8674(79)90367-2. [DOI] [PubMed] [Google Scholar]
  20. Ofek I., Mirelman D., Sharon N. Adherence of Escherichia coli to human mucosal cells mediated by mannose receptors. Nature. 1977 Feb 17;265(5595):623–625. doi: 10.1038/265623a0. [DOI] [PubMed] [Google Scholar]
  21. Reinherz E. L., O'Brien C., Rosenthal P., Schlossman S. F. The cellular basis for viral-induced immunodeficiency: analysis by monoclonal antibodies. J Immunol. 1980 Sep;125(3):1269–1274. [PubMed] [Google Scholar]
  22. Reisner Y., Gachelin G., Dubois P., Nicolas J. F., Sharon N., Jacob F. Interaction of peanut agglutinin, a lectin specific for nonreducing terminal D-galactosyl residues, with embryonal carcinoma cells. Dev Biol. 1977 Nov;61(1):20–27. doi: 10.1016/0012-1606(77)90338-4. [DOI] [PubMed] [Google Scholar]
  23. Rocchi G., Felici A., Ragona G., Heinz A. Quantitative evaluation of Epstein-Barr-virus-infected mononuclear peripheral blood leukocytes in infectious mononucleosis. N Engl J Med. 1977 Jan 20;296(3):132–134. doi: 10.1056/NEJM197701202960302. [DOI] [PubMed] [Google Scholar]
  24. Rosati F., De Santis R. Role of the surface carbohydrates in sperm-egg interaction in Ciona intestinalis. Nature. 1980 Feb 21;283(5749):762–764. doi: 10.1038/283762a0. [DOI] [PubMed] [Google Scholar]
  25. Shen L., Grollman E. F., Ginsburg V. An enzymatic basis for secretor status and blood group substance specificity in humans. Proc Natl Acad Sci U S A. 1968 Jan;59(1):224–230. doi: 10.1073/pnas.59.1.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shepherd V. L., Lee Y. C., Schlesinger P. H., Stahl P. D. L-Fucose-terminated glycoconjugates are recognized by pinocytosis receptors on macrophages. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1019–1022. doi: 10.1073/pnas.78.2.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stahl P. D., Rodman J. S., Miller M. J., Schlesinger P. H. Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1399–1403. doi: 10.1073/pnas.75.3.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stutman O., Dien P., Wisun R. E., Lattime E. C. Natural cytotoxic cells against solid tumors in mice: blocking of cytotoxicity by D-mannose. Proc Natl Acad Sci U S A. 1980 May;77(5):2895–2898. doi: 10.1073/pnas.77.5.2895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tosato G., Magrath I. T., Blaese R. M. T cell-mediated immunoregulation of Epstein Barr virus- (EBV) induced B lymphocyte activation in EBV-seropositive and EBV-seronegative individuals. J Immunol. 1982 Feb;128(2):575–579. [PubMed] [Google Scholar]
  30. Tosato G., Magrath I., Koski I., Dooley N., Blaese M. Activation of suppressor T cells during Epstein-Barr-virus-induced infectious mononucleosis. N Engl J Med. 1979 Nov 22;301(21):1133–1137. doi: 10.1056/NEJM197911223012101. [DOI] [PubMed] [Google Scholar]
  31. Vacquier V. D., Moy G. W. Isolation of bindin: the protein responsible for adhesion of sperm to sea urchin eggs. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2456–2460. doi: 10.1073/pnas.74.6.2456. [DOI] [PMC free article] [PubMed] [Google Scholar]

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