Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1996 Jan;87(1):80–85.

The immunosuppressive compound 2-acetyl-4-tetrahydroxybutyl imidazole inhibits the allogeneic mixed lymphocyte reaction by sequestration of a recirculating subpopulation of T cells.

M G Bradbury 1, K V Doherty 1, C R Parish 1, A B Lyons 1
PMCID: PMC1383971  PMID: 8666439

Abstract

2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) is an immunosuppressive component of caramel food colouring that causes lymphopenia in mice and rats by an unknown mechanism. In this study we investigated some of the affects of THI on the murine immune system. Initially we showed that splenic T lymphocytes from mice treated with 50 mg/l THI in their drinking water were unable to launch a mixed lymphocyte reaction (MLR) against allogeneic stimulator cells, and had decreased and delayed interleukin-2 (IL-2) production. However, these T cells exhibited a normal proliferative response to concanavalin A (Con A), immobilized anti-CD3 monoclonal antibody (mAb) and anti-CD3 plus anti-CD28 mAb. Furthermore, the MLR response could be restored by the addition of IL-2 to the MLR culture. Homing studies using intravenous injection of fluorescence-labelled splenocytes showed that THI treatment decreased absolute numbers of labelled T and B lymphocytes in the blood and the spleen. Furthermore, these labelled cells reappeared in the blood and the spleen when mice were taken off THI, indicating that lymphocyte recirculation and splenic homing were modified reversibly by THI treatment. Cessation of THI treatment also resulted in a rapid reappearance of MLR responsiveness in the spleen, indicating that THI treatment does not functionally impair recirculating T cells. Collectively these data are compatible with the concept that a rapidly recirculating population of T cells, which produce IL-2 in an allogeneic MLR, are lost from the blood and spleen following THI treatment, and are sequestered in other, yet to be identified, tissues.

Full text

PDF
80

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Davidson W. F., Parish C. R. A procedure for removing red cells and dead cells from lymphoid cell suspensions. J Immunol Methods. 1975 Jun;7(2-3):291–300. doi: 10.1016/0022-1759(75)90026-5. [DOI] [PubMed] [Google Scholar]
  2. Gobin S. J., Legg R. F., Paine A. J., Phillips J. A. The effect of 2-acetyl-4-tetrahydroxybutylimidazole on lymphocyte subsets in peripheral blood of the rat. Int J Immunopharmacol. 1989;11(8):937–946. doi: 10.1016/0192-0561(89)90116-1. [DOI] [PubMed] [Google Scholar]
  3. Gobin S. J., Legg R. F., Paine A. J. The role of lymphocyte production and migration in the lymphopenia caused by 2-acetyl-4-tetrahydroxybutyl imidazole. Int J Immunopharmacol. 1992 May;14(4):687–697. doi: 10.1016/0192-0561(92)90132-5. [DOI] [PubMed] [Google Scholar]
  4. Gobin S. J., Phillips J. A. Immunosuppressive effects of 2-acetyl-4-tetrahydroxybutyl imidazole (THI) in the rat. Clin Exp Immunol. 1991 Aug;85(2):335–340. doi: 10.1111/j.1365-2249.1991.tb05729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Harding F. A., McArthur J. G., Gross J. A., Raulet D. H., Allison J. P. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992 Apr 16;356(6370):607–609. doi: 10.1038/356607a0. [DOI] [PubMed] [Google Scholar]
  6. Houben G. F., Penninks A. H. Immunotoxicity of the colour additive caramel colour III; a review on complicated issues in the safety evaluation of a food additive. Toxicology. 1994 Aug 12;91(3):289–302. doi: 10.1016/0300-483x(94)90016-7. [DOI] [PubMed] [Google Scholar]
  7. Houben G. F., van den Berg H., Kuijpers M. H., Lam B. W., van Loveren H., Seinen W., Penninks A. H. Effects of the color additive caramel color III and 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI) on the immune system of rats. Toxicol Appl Pharmacol. 1992 Mar;113(1):43–54. doi: 10.1016/0041-008x(92)90007-f. [DOI] [PubMed] [Google Scholar]
  8. Iscaro A., Mackay I. R., O'Brien C. Lymphopenic effects on mice of a component of ammonia caramel, 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI). Immunol Cell Biol. 1988 Oct-Dec;66(Pt 5-6):395–402. doi: 10.1038/icb.1988.51. [DOI] [PubMed] [Google Scholar]
  9. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  10. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lyons A. B., Parish C. R. Determination of lymphocyte division by flow cytometry. J Immunol Methods. 1994 May 2;171(1):131–137. doi: 10.1016/0022-1759(94)90236-4. [DOI] [PubMed] [Google Scholar]
  12. Mandel T. E., Koulmanda M., Mackay I. R. Prevention of spontaneous and cyclophosphamide-induced diabetes in non-obese diabetic (NOD) mice with oral 2-acetyl-4-tetrahydroxybutylimidazole (THI), a component of caramel colouring III. Clin Exp Immunol. 1992 Jun;88(3):414–419. doi: 10.1111/j.1365-2249.1992.tb06464.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  14. Phillips J. A., Paine A. J. Effect of pyridoxine on the disposition and lymphopenic effects of 2-acetyl-4(5)-tetrahydroxybutyl imidazole in the rat. Xenobiotica. 1990 Jun;20(6):555–562. doi: 10.3109/00498259009046870. [DOI] [PubMed] [Google Scholar]
  15. Sinkeldam E. J., de Groot A. P., van den Berg H., Chappel C. I. The effect of pyridoxine on the number of lymphocytes in the blood of rats fed caramel colour (III). Food Chem Toxicol. 1988 Mar;26(3):195–203. doi: 10.1016/0278-6915(88)90119-6. [DOI] [PubMed] [Google Scholar]
  16. Thuvander A., Oskarsson A. Effects of subchronic exposure to Caramel Colour III on the immune system in mice. Food Chem Toxicol. 1994 Jan;32(1):7–13. doi: 10.1016/0278-6915(84)90030-9. [DOI] [PubMed] [Google Scholar]
  17. Watson J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J Exp Med. 1979 Dec 1;150(6):1510–1519. doi: 10.1084/jem.150.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Weston S. A., Parish C. R. New fluorescent dyes for lymphocyte migration studies. Analysis by flow cytometry and fluorescence microscopy. J Immunol Methods. 1990 Oct 4;133(1):87–97. doi: 10.1016/0022-1759(90)90322-m. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES