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Virchows Archiv B

, 58:389 | Cite as

Immunophenotypic and cell cycle analysis of lymph node cells from dimethylbenzanthracene-treated mice

  • Gary M. Halliday
  • Lois L. Cavanagh
  • H. Konrad Muller
Article

Summary

The chemical carcinogen 7, 12-dimethylbenz(a)anthracene (DMBA) depletes Langerhans cells from murine epidermis. Application of contact sensitizers to DMBA-treated skin induces specific immunological tolerance due to a DMBA-resistant epidermal antigen presenting cell (APC) migrating to local lymph nodes where it presents antigen in a way which activates suppressor cells. As alterations in local lymph node lymphocytes may enhance the ability of the DMBA-resistant APC to activate suppressor cells, these cells were examined in DMBA-treated mice. Lymph nodes in DMBA-treated mice had normal morphology but were larger and contained increased numbers of lymphocytes. Cell cycle analysis revealed that these lymphocytes did not arise from division within the lymph node, suggesting alterations in homing properties of lymphocytes. Contact sensitizer applied to DMBA-treated skin did not increase lymphocyte division, possibly due to suppressor cell inhibition of the development of effector lymphocytes. DMBA treatment had no effect on B cells or Ia expression, but decreased levels of the T lymphocyte cell surface molecule Thy-1, and increased L3T4 and Lyt-2 as quantitated by flow cytofluorimetry. These changes could influence the development of immune responses as these T cell molecules are receptors involved in lymphocyte interactions.

Key words

Chemical carcinogenesis Tumour immunology Cellular immunity Lymph nodes Suppressor lymphocytes 

References

  1. Bhattacharya A, Dorf ME, Springer TA (1981) A shared alloantigenic determinant on Ia antigens encoded by the I-A and I-E subregions: evidence for I region gene duplication. J Immunol 127:2488–2495PubMedGoogle Scholar
  2. Burchiel SW, Hadley WM, Barton SL, Fincher RH, Lauer LD, Dean JH (1988) Persistent suppression of humoral immunity produced by 7,12-dimethylbenz(a)anthracene (DMBA) in B6C3F1 mice: correlation with changes in spleen cell surface markers detected by flow cytometry. Int J Immunopharmacol 10:369–376PubMedCrossRefGoogle Scholar
  3. Chung H-T, Samlowski WE, Kelsey DK, Daynes RA (1986) Alterations in lymphocyte recirculation within ultraviolet light-irradiated mice: efferent blockade of lymphocyte egress from peripheral lymph nodes. Cell Immunol 102:335–345PubMedCrossRefGoogle Scholar
  4. Dennert F, Hyman R, Lesley J, Towbridge IS (1980) Effects of cytotoxic monoclonal antibody specific for T200 glycoprotein on functional lymphoid cell populations. Cell Immunol 53:350–364PubMedCrossRefGoogle Scholar
  5. Dialynas DP, Wilde DB, Marrack P, Pierres A, Wall KA, Havran W, Otten G, Loken MR, Pierres M, Kappler J, Fitch FW (1983) Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK 1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev 74:29–56PubMedCrossRefGoogle Scholar
  6. Fitch F, Lancki D, Havran W (1988) Koch’s postulates and the molecular biology of T-cell function. Immunol Today 9:41–44PubMedCrossRefGoogle Scholar
  7. Gallatin M, St John TP, Seigelman M, Reichert R, Butcher EC, Weissman IL (1986) Lymphocyte homing receptors. Cell 44:673–680PubMedCrossRefGoogle Scholar
  8. Gunter KC, Malek TR, Shevach EM (1984) T cell activating properties of an anti-Thy-1 monoclonal antibody: possible analogy to OKT3/LEU-4. J Exp Med 159:716–730PubMedCrossRefGoogle Scholar
  9. Halliday GM, Muller HK (1984) The role of the Langerhans cell in local defence. IRCS J Med Sci 12:567–569Google Scholar
  10. Halliday GM, Muller HK (1986) Induction of tolerance via skin depleted of Langerhans cells by a chemical carcinogen. Cell Immunol 99:220–227PubMedCrossRefGoogle Scholar
  11. Halliday GM, Muller HK (1987a) Langerhans cell presentation of sheep red blood cells induces antibody production. Immunol Cell Biol 65:71–76PubMedCrossRefGoogle Scholar
  12. Halliday GM, Muller HK (1987b) Sensitization through carcinogen-induced Langerhans cell-deficient skin activates specific long lived suppressor cells for both cellular and humoral immunity. Cell Immunol 109:206–221PubMedCrossRefGoogle Scholar
  13. Halliday GM, MacCarrick GR, Muller HK (1987) Tumour promotors but not initiators deplete Langerhans cells from murine epidermis. Br J Cancer 56:328–330PubMedGoogle Scholar
  14. Halliday GM, Cavanagh LL, Muller HK (1988b) Antigen presented in the local lymph node by cells from dimethylbenzanthracene treated murine epidermis activates suppressor cells. Cell Immunol 117:289–302PubMedCrossRefGoogle Scholar
  15. Halliday GM, Odling KA, Ruby JC, Muller HK (1988 a) Suppressor cell activation and enhanced skin allograft survival after tumor promotor but not initiator induced depletion of cutaneous Langerhans cells. J Invest Dermatol 90:293–297PubMedCrossRefGoogle Scholar
  16. Janeway CA, Haque S, Smith LA, Saizawa K (1987) The role of the murine L3T4 molecule in T cell activation: differential effects of anti-L3T4 on activation by monoclonal anti-receptor antibodies. J Mol Cell Immunol 3:121–127PubMedGoogle Scholar
  17. Kroczek RA, Gunter KC, Seligmann B, Shevach EM (1986) Induction of T cell activation by monoclonal anti-Thy-1 antibodies. J Immunol 136:4376–4384Google Scholar
  18. McArdle JP, Knight BA, Halliday GM, Muller HK, Rowden G (1986) Quantitative assessment of Langerhans cells in actinic keratosis, Bowen’s disease, keratoacanthoma, squamous cell carcinoma and basal cell carcinoma. Pathology 18:212–216PubMedCrossRefGoogle Scholar
  19. Muller HK, Halliday GM (1989) The skin immune system and immunosurveillance. In: Bos JD (ed) The skin immune system. CRC Press Inc, Boca Raton, FL, pp 451–464Google Scholar
  20. Müller HK, Halliday GM, Knight BA (1985) Carcinogen induced depletion of cutaneous Langerhans cells. Br J Cancer 52:81–85PubMedGoogle Scholar
  21. Noonan FP, De Fabo EC (1985) Immune suppression of ultraviolet radiation and its role in ultraviolet radiation induced carcinogenesis in mice. Aust J Dermatol 26:4–8CrossRefGoogle Scholar
  22. Odling KA, Halliday GM, Muller HK (1987) Enhanced survival of skin grafts depleted of Langerhans cells by treatment with dimethy lbenzanthracene. Immunology 62:379–385PubMedGoogle Scholar
  23. Rowden G (1981) The Langerhans cell. CRC Crit Rev Immunol 3:95–180Google Scholar
  24. Ruby JC, Halliday GM, Muller HK (1989) Differential effects of benzo(a)pyrene and dimethylbenz(a)anthracene on Langerhans cells distribution and contact sensitization in murine epidermis. J Invest Dermatol 92:150–155PubMedCrossRefGoogle Scholar
  25. Sarmiento M, Glasebrook AL, Fitch FW (1980) IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol 125:2665–2672PubMedGoogle Scholar
  26. Silberberg-Sinakin I, Thorbecke GJ (1980) Contact hypersensitivity and Langerhans cells. J Invest Dermatol 75:61–67PubMedCrossRefGoogle Scholar
  27. Sprent J, Webb SR (1987) Function and specificity of T cell subsets in the mouse. Adv Immunol 41:39–133PubMedCrossRefGoogle Scholar
  28. Stingl G, Katz SI, Clement L, Green I, Shevach EM (1978) Immunologic functions of Ia-bearing epidermal Langerhans cells. J Immunol 121:2005–2013PubMedGoogle Scholar
  29. Taylor IW, Milthorpe BK (1980) An evaluation of DNA fluorochromes, staining techniques and analysis for flow cytometry. J Histochem Cytochem 28:1224–1232PubMedGoogle Scholar
  30. Unanue ER, Beller DI, Lu CY, Allen PM (1984) Antigen presentation: Comments on its regulation and mechanism. J Immunol 132:1–5PubMedGoogle Scholar
  31. Weiss A, Imboden JB (1987) Cell surface molecules and early events involved in human T lymphocyte activatiton. Adv Immunol 41:1–38PubMedGoogle Scholar
  32. Williams AF, Gagnon J (1982) Neuronal cell Thy-1 glycoprotein: homology with immunoglobulin. Science 216:696–703PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Gary M. Halliday
    • 1
  • Lois L. Cavanagh
    • 1
  • H. Konrad Muller
    • 2
  1. 1.Department of Medicine (Dermatology)University of SydneyNew South WalesAustralia
  2. 2.Department of PathologyUniversity of TasmaniaTasmaniaAustralia

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