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Immunotoxicology and Allergy: Options for Ex Vivo and In Vitro Experimentation

  • Philip A. Botham
  • Ian Kimber
Chapter

Abstract

The purpose of this review is to identify the potential benefits and limitations of in vitro and ex vivo techniques in the identification of immunotoxicants and allergens, and in the investigation of the mechanisms through which chemicals perturb immune function.

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REFERENCES

  1. 1.
    Trizio, D., Basketter, D.A., Botham, P.A., Graepel, P.H., Lambre, C., Magda, S.J., Pal, T.M., Riley, A.J., Ronneberger, H., Van Sittert, N.J. & Bontinck, W.J. (1988). Identification of immunotoxic effects of chemicals and assessment of their relevance to man. Food and Chemical Toxicology 26, 527–539.PubMedCrossRefGoogle Scholar
  2. 2.
    Cupps, T.R. & Fauci, A.S. (1982). Corticosteroid-mediated immunoregulation in man. Immunological Reviews 65, 133–155.PubMedCrossRefGoogle Scholar
  3. 3.
    Heise, E.R. (1982). Diseases associated with immunosuppression. Environmental Health Perspectives 43, 9–19.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Penn, I. (1985). Neoplastic consequences of immunosuppression. In Immunotoxicology and Immunopharmacology (ed. J.H. Dean, M.I. Luster, A.E. Munson & H. Amos), pp. 79–89. New York: Raven Press.Google Scholar
  5. 5.
    Descotes, J., ed. (1986). Immunotoxicology of Drugs and Chemicals. Amsterdam: Elsevier.Google Scholar
  6. 6.
    Vos, J.G., de Klerk, A., Krajnc, E.I., Kruizinga, W., van Ommen, B. & Rozing, J. (1984). Toxicity of bis (tributyltin) oxide in the rat. II. Suppression of thymus-dependent immune responses and of parameters on nonspecific resistance after short-term exposure. Toxicology and Applied Pharmacology 75, 387–408.PubMedCrossRefGoogle Scholar
  7. 7.
    Vos, J.G., de Klerk, A. & Krajnc, E.I. (1985). Immunotoxicology of bis (tri-n-butyltin) oxide after long-term exposure of rats. The Toxicologist 5, 5.Google Scholar
  8. 8.
    Luster, M.I., Munson, A.E., Thomas, P.T., Hosapple, M.P., Fenters, J.D., White, K.L., Lauer, L.D., Germolec, D.R., Rosenthal, G.J. & Dean, J.H. (1988). Development of a testing battery to assess chemical-induced immunotoxicity: National Toxicology Program’s guidelines for immunotoxicity evaluation in mice. Fundamental and Applied Toxicology 10, 2–19.PubMedCrossRefGoogle Scholar
  9. 9.
    Greenlee, W.F., Dold, K.M., Irons, R.D. & Osborne, R. (1985). Evidence for direct action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thymic epithelium. Toxicology and Applied Pharmacology 79, 112–120.PubMedCrossRefGoogle Scholar
  10. 10.
    Cook, J.C., Dold, K.M. & Greenlee, W.F. (1987). An in vitro model for studying the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to human thymus. Toxicology and Applied Pharmacology 89, 256–268.PubMedCrossRefGoogle Scholar
  11. 11.
    Meredith, C., Scott, M.P. & Miller, K. (1989). Immunotoxicology screening in vitro: modulation of expression of immunoregulatory genes. Human Toxicology 8, 411–412.CrossRefGoogle Scholar
  12. 12.
    Dean, J.H., Thurmond, L.M. & Rosenbaum, D.J. (1986). Immunotoxicology: reduced animal usage through the use of in vitro lymphoid cell models. In Proceedings of Seminar on Chemical Testing and Animal Welfare, 232–248. Stockholm: National Chemicals Incorporate.Google Scholar
  13. 13.
    Magnusson, B. & Kligman, A.M. (1970). Allergic Contact Dermatitis in the Guinea-pig. Springfield, IL, USA: Charles. C. Thomas.Google Scholar
  14. 14.
    Buehler, E.V. (1965). Delayed contact hypersensitivity in the guinea-pig. Archives of Dermatology 91, 171–177.PubMedCrossRefGoogle Scholar
  15. 15.
    Oliver, G.J.A., Botham, P.A. & Kimber, I. (1986). Models for contact sensitisation—novel approaches and future developments. British Journal of Dermatology 115, 53–62.PubMedCrossRefGoogle Scholar
  16. 16.
    Kimber, I. (1989). Aspects of the immune response to contact allergens: opportunities for the development and modification of predictive test methods. Food and Chemical Toxicology 27, 755–762.PubMedCrossRefGoogle Scholar
  17. 17.
    Gad, S.C., Dunn, B.J., Dobbs, D.W., Reilly, C., & Walsh, R.D. (1986). Development and validation of an alternative dermal sensitization test: the mouse ear swelling test (MEST). Toxicology and Applied Pharmacology 84, 93–114.PubMedCrossRefGoogle Scholar
  18. 18.
    Maisey, J. & Miller, K. (1986). Assessment of the ability of mice fed on vitamin A supplemented diet to respond to a variety of potential contact sensitizers. Contact Dermatitis 15, 17–23.PubMedCrossRefGoogle Scholar
  19. 19.
    Descotes, J. (1988). Identification of contact allergens: the mouse ear sensitization assay. Journal of Toxicology—Cutaneous and Ocular Toxicology 7, 263–272.CrossRefGoogle Scholar
  20. 20.
    Kimber, I., Mitchell, J.A. & Griffith, A.C. (1986). Development of a murine local lymph node assay for determination of sensitizing potential. Food and Chemical Toxicology 24, 585–586.CrossRefGoogle Scholar
  21. 21.
    Kimber, I., Hilton, J. & Weisenberger, C. (1989). The murine local lymph node assay for identification of contact allergens: a preliminary evaluation of in situ measurement of lymphocyte proliferation. Contact Dermatitis 21, 215–220.PubMedCrossRefGoogle Scholar
  22. 22.
    Kimber, I., Hilton, J. & Botham ,P.A. (1990). Identification of contact allergens using the murine local lymph node assay: comparisons with the Beuhler occluded patch test in guinea-pigs. Journal of Applied Toxicology 10, 173–180.PubMedCrossRefGoogle Scholar
  23. 23.
    Kimber, I., Hilton, J., Botham, P.A., Basketter, D.A., Scholes, E.W., Miller, K., Robbins, M.C., Harrison, P.T.C., Gray, T.J.B. & Waite, S.J. (1991). The murine local lymph node asssay: results of an interlaboratory trial. Toxicology Letters, 55, 203–213.PubMedCrossRefGoogle Scholar
  24. 24.
    Kimber, I. & Weisenberger, C. (1989). A murine local lymph node assay for the identification of contact allergens: assay development and results of an initial validation study. Archives of Toxicology 63, 274–282.PubMedCrossRefGoogle Scholar
  25. 25.
    Oort, J. & Turk, J.L. (1965). A histological and autoradiographic study of lymph nodes during the development of contact sensitivity in guinea-pigs. British Journal of Experimental Pathology 46, 147–154.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Parrott, D.M.V. & de Sousa, M.A.B. (1966). Changes in the thymus-dependent areas of lymph nodes after immunological stimulation. Nature, London 212, 1316–1317.CrossRefGoogle Scholar
  27. 27.
    Turk, J.L. (1967). Cytology of the induction of hypersensitivity. British Medical Bulletin 23, 3–8.PubMedGoogle Scholar
  28. 28.
    Knight, S.C., Krejci, J., Malkovsky, M., Colizzi, V., Gautam, A. & Asherson, G.L. (1985). The role of dendritic cells in the initiation of immune responses to contact sensitizers. I. In vivo exposure to antigen. Cellular Immunology 94, 427–434.PubMedCrossRefGoogle Scholar
  29. 29.
    Knight, S.C., Bedford, P. & Hunt, R. (1985). The role of dendritic cells in the initiation of immune responses to contact sensitizers. II. Studies in nude mice. Cellular Immunology 94, 435–439.PubMedCrossRefGoogle Scholar
  30. 30.
    Macatonia, S.E., Edwards, A.J. & Knight, S.C. (1986). Dendritic cells and the initiation of contact sensitivity to fluorescein isothiocyanate. Immunology 59, 509–514.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Katz, D.R., Mukherjee, S., Maisey, J. & Miller, K. (1987). Vitamin A acetate as a regulator of accessory cell function in delayed type hypersensitivity responses. International Archives of Allergy and Applied Immunology 82, 53–56.PubMedCrossRefGoogle Scholar
  32. 32.
    Kinnaird, A., Peters, S.W., Foster, J.R. & Kimber, I. (1989). Dendritic cell accumulation in draining lymph nodes during the induction phase of contact allergy in mice. International Archives of Allergy and Applied Immunology 89, 202–210.PubMedCrossRefGoogle Scholar
  33. 33.
    Macatonia, S.E., Knight, S.C., Edwards, A.J., Griffiths, S. & Fryer, P, (1987). Localisation of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothicoyanate: functional and morphological studies. Journal of Experimental Medicine 166, 1654–1667.PubMedCrossRefGoogle Scholar
  34. 34.
    Jones, D.A., Morris, A.G. & Kimber, I. (1989). Assessment of the functional activity of antigen-bearing dendritic cells isolated from the lymph nodes of contact-sensitized mice. International Archives of Allergy and Applied Immunology 90, 230–236.PubMedCrossRefGoogle Scholar
  35. 35.
    Hopkins, S.J., Humphreys, M., Kinnaird, A., Jones, D. & Kimber, I. (1989). Early production of IL-1 by draining lymph node cells following contact sensitization. Cytokines 1, 108.Google Scholar
  36. 36.
    Moval, H.Z. (1985). The Inflammatory Reaction. Amsterdam: Elsevier.Google Scholar
  37. 37.
    Kimber, I., Ward, R.K., Shepherd, C.J., Smith, M.N., McAdam, K.P.W.J. & Raynes, J.G. (1989). Acute-phase proteins and the serological evaluation of experimental contact sensitivity in the mouse. International Archives of Allergy and Applied Immunology 89, 149–155.PubMedCrossRefGoogle Scholar
  38. 38.
    Marinkovic, S., Jahreis, G.P., Wong, G.G. & Baumann, H. (1989). IL-6 modulates the synthesis of a specific set of acute phase plasma proteins in vivo. Journal of Immunology 142, 808–812.Google Scholar
  39. 39.
    Kimber, I., Cumberbatch, M., Humphreys, M. & Hopkins, S.J. (1990). Contact hypersensitivity induces plasma interleukins 6 (IL-6). International Archives of Allergy and Applied Immunology 92, 97–99.PubMedCrossRefGoogle Scholar
  40. 40.
    Kimber, I., Cumberbatch, M. & Coleman, J.W. (1990). Serum histamine and the elicitation of murine contact sensitivity. Journal of Applied Toxicology, in press.Google Scholar
  41. 41.
    Phanuphak, P., Moorhead, J.W. & Claman, H.N. (1974). Tolerance and contact sensitivity to DNFB in mice. I. In vivo detection of ear swelling and correlation with in vitro cell stimulation. Journal of Immunology 112, 115–123.Google Scholar
  42. 42.
    Kimber, I., Botham, P.A., Rattray, N.J. & Walsh, S.T. (1986). Contact sensitizing and tolerogenic properties of 2,4-dinitrothiocyanobenzene. International Archives of Allergy and Applied Immunology 81, 258–264.PubMedCrossRefGoogle Scholar
  43. 43.
    Robinson, M.K. (1989). Optimization of an in vitro lymphocyte blastogenesis assay for predictive assessment of immunologic responsiveness to contact sensitizers. Journal of Investigative Dermatology 92, 860–867.PubMedCrossRefGoogle Scholar
  44. 44.
    Hauser, C. & Katz, S.I. (1988). Activation and expansion of hapten and protein-specific T helper cells from non-sensitized mice. Proceedings of the National Academy of Sciences of the United States of America 85, 5625–5628.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Roberts, D.W. & Williams, D.L. (1982). The derivation of quantitative correlations between skin sensitization and physicochemical parameters for alkylating agents, and their application to experimental data for sultones. Journal of Theoretical Biology 99, 807–811.PubMedCrossRefGoogle Scholar
  46. 46.
    Roberts, D.W., Goodwin, B.J., Williams, D.L., Jones, K., Johnson, A.W. & Alderson, J.C.E. (1983). Correlations between skin sensitisation potential and chemical reactivity for p-nitrobenzyl compounds. Food and Chemical Toxicology 21, 811–813.PubMedCrossRefGoogle Scholar
  47. 47.
    Basketter, D.A. (1989). Quantitative structure-activity relationships. Toxicology in Vitro 3, 351–353.PubMedCrossRefGoogle Scholar
  48. 48.
    Basketter, D.A. & Roberts, D.W. (1990). Structure-activity relationships in contact allergy. International Journal of Cosmetic Science 12, 81–90.PubMedCrossRefGoogle Scholar
  49. 49.
    Karol, M.H., Dixon, C, Brady, M. & Alarie, Y. (1990). Immunologic sensitization and pulmonary hypersensitivity by repeated inhalation of aromatic isocyanates. Toxicology and Applied Pharmacology 53, 260–270.CrossRefGoogle Scholar
  50. 50.
    Karol, M.H. (1983). Concentration-dependent immunologic response to toluene diisocyan-ate (TDI) following inhalation exposure. Toxicology and Applied Pharmacology 68, 229–241.PubMedCrossRefGoogle Scholar
  51. 51.
    Karol, M.H., Stadler, J. & Magreni, C. (1985). Immunotoxologic evaluation of the respiratory system: animal models for immediate- and delayed-onset pulmonary hypersensitivity. Fundamental and Applied Toxicology 5, 459–472.PubMedCrossRefGoogle Scholar
  52. 52.
    Botham, P.A., Hext, P.M., Rattray, N.J., Walsh, S.T. & Woodcock, D.R. (1988). Sensitisation of guinea-pigs by inhalation exposure to low molecular weight chemicals. Toxicology Letters 41, 159–173.PubMedCrossRefGoogle Scholar
  53. 53.
    Botham, P.A., Rattray, N.J., Woodcock, D.R., Walsh, S.T. & Hext, P.M. (1989). The induction of respiratory allergy in guinea-pigs following intradermal injection of trimellitic anhydride: a comparison with the response to 2,4-dinitrochlorobenzene. Toxicology Letters 47, 25–39.PubMedCrossRefGoogle Scholar
  54. 54.
    Kammuller, M.E. & Seinen, W, (1988). Structural requirements for hydantoins and 2-thiohydantoins to induce lymphoproliferative popliteal lymph node reactions in the mouse. International Journal of Immunopharmacology 10, 997–1010.PubMedCrossRefGoogle Scholar
  55. 55.
    Kammuller, M.E., Thomas, C, De Bakker, J.M., Bloksma, N. & Seinen, W. (1989). The popliteal lymph node assay in mice to screen for the immune disregulating potential of chemicals—a preliminary study. International Journal of Immunopharmacology 11, 293–300.PubMedCrossRefGoogle Scholar
  56. 56.
    Gleichmann, E., Kimber, I. & Purchase, I.F.H. (1989). Immunotoxicology: suppressive and stimulating effects of drugs and chemicals on the immune system. Archives of Toxicology 63, 257–273.PubMedCrossRefGoogle Scholar
  57. 57.
    Exon, J.H., Koller, L.D., Talcott, P.A., O’Reilly, C.A. & Henningsen, G.M. (1986). Immunotoxicity testing: an economical multiple-assay approach. Fundamental and Applied Toxicology 7, 387–397.PubMedCrossRefGoogle Scholar
  58. 58.
    Vos, J.G. & van Loveren, H. (1987). Immunotoxicity testing in the rat. In Advances in Modern Environmental Toxicology, Vol. 8, Environmental Chemical Exposure and Immune System Integrity (ed. M.A. Mehlman), pp. 147–159. Princeton, NJ: Princeton Scientific.Google Scholar
  59. 59.
    Luster, M.I., Munson, A.E., Thomas, P.T., Hosapple, M.P., Fanters, J.D., White, K.L., Lauer, L.D., Germolc, D.R., Rosenthall, G.J. & Dean, J.H. (1988). Methods evaluation: development of a testing battery to assess chemical-induced immunotoxicity (National Toxicology Programme guidelines for immunotoxicity evaluation in mice). Fundamental and Applied Toxicology 10, 2–19.PubMedCrossRefGoogle Scholar
  60. 60.
    Offner, H. & Clausen, J. (1974). Inhibition of lymphocyte response to stimulants by unsaturated fatty acids and prostglandins. Lancet ii, 400–401.CrossRefGoogle Scholar
  61. 61.
    Mertin, J. & Hughes, D. (1975). Specific inhibitory action of polyunsaturated fatty acids on lymphocyte transformation induced by PHA and PPD. International Archives of Allergy and Applied Immunology 48, 203–210.PubMedCrossRefGoogle Scholar
  62. 62.
    Tsang, W.M., Weyman, C. & Smith, A.D. (1977). The effect of fatty acids and albumin on the transformation of rodent spleen lymphocytes stimulated by phytohaemagglutinin, concanavalin A or bacterial lipopolysaccharide. Biochemical Society Transactions 5, 1159– 1160.PubMedCrossRefGoogle Scholar
  63. 63.
    Mertin, J. (1976). Effect of polyunsaturated fatty acids on skin allograft survival and primary and secondary cytotoxic response in mice. Transplantation 21, 1–4.PubMedCrossRefGoogle Scholar
  64. 64.
    Friend, J.V., Lock, S.O., Gurr, M.I. & Parish, W.E. (1980). Effect of dietary lipids on the immune response of Hartley strain guinea-pigs. International Archives of Allergy and Applied Immunology 62, 292–301.PubMedCrossRefGoogle Scholar
  65. 65.
    Parish, W.E. (1986). Evaluation of in vitro predictive tests for irritation and allergic sensitisation. Food and Chemical Toxicology 24, 481–494.PubMedCrossRefGoogle Scholar
  66. 66.
    Kimber, I., Hilton, J., Weisenberger, C. (1989). The murine local lymph node assay for identification of contact allergens: a preliminary evaluation of in situ measurement of lymphocyte proliferation. Contact Dermatitis 21, 215–220.PubMedCrossRefGoogle Scholar
  67. 67.
    Kimber, I., Hilton, J. & Botham, P.A. (1990). Identification of contact allergens using the murine local lympho node assay: comparisons with the Buehler occluded patch test in guinea-pigs. Journal of Applied Toxicology 10, 173–180.PubMedCrossRefGoogle Scholar
  68. 68.
    Parish, W.E. (1986). Evaluation of in vitro predictive tests for irritation and allergic sensitisation. Food and Chemical Toxicology 24, 481–494.PubMedCrossRefGoogle Scholar

Copyright information

© FRAME 1991

Authors and Affiliations

  • Philip A. Botham
    • 1
  • Ian Kimber
    • 1
  1. 1.ICI Central Toxicology LaboratoryMacclesfieldUK

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