Folia Microbiologica

, Volume 18, Issue 5, pp 393–401 | Cite as

The production of migration inhibitory factor (MIF) in rabbit lymphocytes by other than immunological mechanism

  • J. Pekárek
  • J. Švejcar
  • V. Hříbalová
  • J. Johanovský


The ability of certain substances to activate lymphocytes in terms of the production of biologically active substances was studied. These substances were tested by following their migration inhibitory activity. The capacity of concanavalin A and commercial preparations of phytohaemagglutinin (PHA-M and PHA-P) to induce formation of MIF was confirmed. In addition, similar activities were found even in antirabbit antilymphocyte serum (ALS) and erythrogenic toxin (ET). The production of MIF was usually found in material obtained from rabbits treated with complete Freund adjuvant (CFA). On the other hand, material obtained from non-treated rabbits, was found to be inactive with the exception of thymus from young rabbits. The results support the significance of an increasing pharmacological potency of cells in the course of sensitization with CFA. The evidence concerning the release of MIF by ET was extended by similar finding in rabbits made tolerant to the pyrogenic activity of this particular toxin. Lymphocytes obtained from rabbits that were unable to respond to ET by fever, could not liberate MIF (at the same time) upon incubation with ET, even though these lymphocytes produced MIF normally after incubation with PPD tuberculin or concanavalin A. The importance of these results is discussed in terms of the immunologically nonspecific activation of lymphocytes that can mimic immunologically specific events.


Migration Inhibitory Factor Scarlet Fever Young Rabbit Endogenous Pyrogen Scarlet Fever Toxin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Atkins E., Feldman J. D., Francis L., Hursh E.: Studies on the mechanism of fever accompanying delayed hypersensitivity. The role of the sensitized lymphocyte.J. Exptl. Med. 135, 1113 (1972).CrossRefGoogle Scholar
  2. Bloom B. R.:In vitro approaches to the mechanism of cell-mediated immune reactions.Adv. Immunol. 13, 101 (1971).PubMedGoogle Scholar
  3. Castrová A., Pekárek J., Johanovský J.: Pyrogenic activity of antilymphocyte and of antipolymorphonuclear sera.Z. Immun. Forsch. 144, 221 (1972).Google Scholar
  4. Cooke J. V.: Scarlet fever: VII. The course of the development of immunity in scarlet fever.Am. J. Dis. Children 35, 983 (1928).Google Scholar
  5. Cremer N., Watson D. W.: Host-parasite factors in group A streptococcal infections. A comparative study of streptococcal pyrogenic toxins and gram-negative bacterial endotoxins.J. Exptl. Med. 112, 1037 (1960).CrossRefGoogle Scholar
  6. Diengdoh J. V., Turk J. L.: Immunological significance of lysosomes within lymphocytesin vivo.Nature (London)207, 1405 (1965).CrossRefGoogle Scholar
  7. Dochez A. R., Stevens F. A.: Studies on the biology of streptococcus. VII. Allergic reactions with strains from erysipelas.J. Exptl. Med. 46, 487 (1927).CrossRefGoogle Scholar
  8. Epstein L. B., Cline M. J., Merigan T. C.: The interaction of human macrophages and lymphocytes in the phytohemagglutinin-stimulated production of interferon.J. Clin. Invest. 50, 744 (1971).PubMedCrossRefGoogle Scholar
  9. Falk R. E., Falk J. A.: The reactivity of non-sensitized thymocytes to antigen. The release of antigen specific lymphocyte activating substances, 5th Leucocyte Culture Conf. (Academic Press, N.Y.) p. 649 (1970).Google Scholar
  10. Granger G. A., Kolb W. P.: Lymphocytein vitro cytotoxicity: Mechanism of immune and non-immune small lymphocyte mediated target L cell destruction.Immunology 101, 111 (1968).Google Scholar
  11. Gräsbeck R., Nordman C., De La Chapelle A.: Mitogenic action of antilymphocyte immune serum on peripheral leucocytesin vitro.Lancet ii, 385 (1963).CrossRefGoogle Scholar
  12. Hanna E. E., Watson D. W.: Host-parasite relationships among group A streptococci. IV. Suppression of antibody response by streptococcal pyrogenic exotoxin.J. Bacteriol. 95, 14 (1968).PubMedGoogle Scholar
  13. Hříbalová V., Pospíšil M.: Lymphocyte-stimulating activity of scarlet fever toxin.Experientia 29, 704 (1973).PubMedCrossRefGoogle Scholar
  14. Kaplan J.: Staphylococcal enterotoxin B induced release of macrophage migration inhibition factor from normal lymphocytes.Cell. Immunol. 3, 245 (1972).PubMedCrossRefGoogle Scholar
  15. Kim Y. B., Watson D. W.: A purified group A streptococal pyrogenic exotoxin. Physicochemical and biological properties including the enhancement of susceptibility to endotoxin lethal shock.J. Exptl. Med. 131, 611 (1970).CrossRefGoogle Scholar
  16. Lamelin J. P., Vassali P.: Inhibition of macrophage migration by a soluble factor from lymphocytes stimulated with PHA or ALS.Nature 229, 426 (1971).PubMedCrossRefGoogle Scholar
  17. Lawrence H. S., Landy M.: Mediators of cellular immunity. Academic Press, N.Y. (1969).Google Scholar
  18. Pekárek J., Švejcar J., Johanovský J.: The inhibition of migration inhibiting factor formation by various antilymphocyte sera.Immunology 20, 895 (1971).PubMedGoogle Scholar
  19. Pick E., Krejčí J., Turk J. L.: Release of skin reactive factor from guinea-pig lymphocytes by mitogens.Nature 225, 236 (1970a).PubMedCrossRefGoogle Scholar
  20. Pick E., Brostoff J., Krejčí J., Turk J. L.: Interaction between “sensitized lymphocytes”, and antigenin vitro. II. Mitogen-induced release of skin reactive and macrophage migration inhibitory factors.Cell Immun. 1, 92 (1970b).CrossRefGoogle Scholar
  21. Remold H. G., David J. R.: Cellular immunity: Characterization of migration inhibitory factor (MIF) from guinea-pig lymphocytes stimulated with concanavalin A. Proc. VIth Leucocyte Culture Conference (Academic Press, N.Y., p. 22) (1971).Google Scholar
  22. Schuh V.: The pyrogenic effect of scarlet fever toxin. I. Neutralization with antitoxin; the nature of tolerance.Folia Microbiol. 10, 156 (1965).Google Scholar
  23. Schuh V., Hříbalová V.: The pyrogenic effect of scarlet fever toxin. II. Leucocytic pyrogen formation induced by scarlet fever toxin orSalmonella paratyphi B endotoxin.Folia Microbiol. 11, 112 (1966).Google Scholar
  24. Schuh V., Hříbalová V., Atkins E.: The pyrogenic effect of scarlet fever toxin. IV. Pyrogenicity of strain C 203 U filtrate: Comparison with some basic characteristics of the known types of scarlet fever toxin.Yale J. Biol. Med. 43, 31 (1970).PubMedGoogle Scholar
  25. Schwartz H. J., Leon M. A., Pelley R. P.: Concanavalin A-induced release of skin factor from lymphoid cells.J. Immunol. 104, 265 (1970).PubMedGoogle Scholar
  26. Stock A. H.: Studies on hemolytic streptococcus. IV. Further purification and concentration of scarlet fever toxin.J. Biol. Chem. 142, 777 (1942).Google Scholar
  27. Suter E., Ullman G. E., Hoffman R. G.: Sensitivity of mice to endotoxin after vaccination with BCG.Proc. Soc. Exptl. Biol. Med. 99, 167 (1958).Google Scholar
  28. Švejcar J., Johanovský J., Pekárek J.: VI. Effect of endotoxin on the course and results of spleen cell migration in normal and tuberculin hypersensitive guina-pigs.Z. Immun. Forsch. 132, 165 (1967).Google Scholar
  29. Švejcar J., Pekárek J., Johanovský J.: Studies on production of biologically active substance which inhibit cell migration in supernatants and extracts of hypersensitive lymphoid cells incubated with specific antigenin vitro.Immunology 16, 1 (1968).Google Scholar
  30. Švejcar J., Pekárek J., Johanovský J.: Effect of various antilymphocyte sera on the migration of spleen cells.Immunology 21, 45 (1971a).PubMedGoogle Scholar
  31. Švejcar J., Pekárek J., Johanovský J.: XIV. Species nonspecificity of biologically active substances (migration inhibitory factor) released during the interaction of hypersensitive lymphocytes with antigenin vitro.Z. Immun. Forsch. 141, 119 (1971b).Google Scholar
  32. Vejbora O., Johanovský J., Vrána M.: Dynamics of changes in specific hypersensitivity to endotoxin in BCG sensitized mice.Folia Microbiol. 6, 370 (1961).CrossRefGoogle Scholar
  33. Vincent C., Gariazzo M. J.: Détection du MIF humain produit après stimulation par le sérum antilymphocytaire. Cours International de Transplantation, Lyon, p. 369 (1971).Google Scholar
  34. Watson D. W.: Host-parasite factors in group A streptococcal infections. Pyrogenic and other effects of immunologic distinct exotoxins related to scarlet fever toxins.J. Exptl. Med. 111, 255 (1960).CrossRefGoogle Scholar
  35. Watson D. W., Kim Y. B.: Modification of host responses to bacterial endotoxins. I. Specificity of pyrogenic tolerance and the role of hypersensitivity in pyrogenicity, lethality, and skin reactivity.J. Exptl. Med. 118, 425 (1963).CrossRefGoogle Scholar

Copyright information

© Institute of Microbiology, Academy of Sciences of the Czech Republic 1973

Authors and Affiliations

  • J. Pekárek
    • 1
    • 2
  • J. Švejcar
    • 1
    • 2
  • V. Hříbalová
    • 1
    • 2
  • J. Johanovský
    • 1
    • 2
  1. 1.Institute of Sera and VaccinesPrague 10
  2. 2.Institute of Hygiene and EpidemiologyPrague 10

Personalised recommendations