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Immunology logoLink to Immunology
. 1989 Sep;68(1):51–58.

Regulation of delayed-type hypersensitivity-like responses in the mouse lung, determined with histological procedures: serotonin, T-cell suppressor-inducer factor and high antigen dose tolerance regulate the magnitude of T-cell dependent inflammatory reactions.

J Garssen 1, F P Nijkamp 1, S S Wagenaar 1, A Zwart 1, P W Askenase 1, H Van Loveren 1
PMCID: PMC1385504  PMID: 2807371

Abstract

We have studied delayed-type hypersensitivity (DTH) responses to picryl chloride (PCl) in the lungs of mice. Intranasal challenge with 0.6% picryl sulphonic acid (PSA), a water soluble form of PCl, of BALB/c mice, sensitized with PCl epicutaneously 1 week earlier, induced an accumulation of mononuclear inflammatory cells around bronchioli and blood vessels. Maximal inflammatory responses were seen 48 hr after challenge. These responses were antigen-specific, and also T-cell dependent, since athymic nude mice failed to show this reaction. A role for mast cells in the responses was studied using two strains of mast cell-deficient mice. In one of these (W/Wv) lung DTH responses to PCl were reduced severely. In the other strain (S1/S1d) the responses around vessels were decreased slightly, whereas the responses in the interstitial tissue and around bronchioli were similar to those in +/+ littermate controls. Involvement of serotonin was investigated using two serotonin receptor antagonists, i.e. methysergide and ketanserin. Treatment of mice with either of the antagonists prevented occurrence of the DTH-like reaction in the lung after intranasal antigen challenge. In the lungs of sensitized mice, significantly increased permeability was established 2 hr after antigen challenge. It was concluded that release of serotonin in the lung may provide an environment that comprises local vascular permeability and that facilitates the local recruitment and possibly the activation of DTH effector T cells, leading to subsequent attraction of mononuclear leucocytes into the lung. Immunological regulation of the DTH-like reactions in the lung was similar to that of contact sensitivity in the skin, since intravenous injection of an antigen-specific T-cell suppressor inducer factor prior to sensitization or pretreatment with a high dose of picryl sulphonic acid intravenously both resulted in reduction of the DTH-like lung histological response to picryl sulphonic acid. From these findings it was concluded that DTH-like lung responses are similar to DTH responses in the skin.

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Selected References

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  1. Askenase P. W., Rosenstein R. W., Ptak W. T cells produce an antigen-binding factor with in vivo activity analogous to IgE antibody. J Exp Med. 1983 Mar 1;157(3):862–873. doi: 10.1084/jem.157.3.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Askenase P. W., Van Loveren H., Kraeuter-Kops S., Ron Y., Meade R., Theoharides T. C., Nordlund J. J., Scovern H., Gerhson M. D., Ptak W. Defective elicitation of delayed-type hypersensitivity in W/Wv and SI/SId mast cell-deficient mice. J Immunol. 1983 Dec;131(6):2687–2694. [PubMed] [Google Scholar]
  3. Enander I., Ahlstedt S., Nygren H., Björkstén B. Sensitizing ability of derivatives of picryl chloride after exposure of mice on the skin and in the lung. Int Arch Allergy Appl Immunol. 1983;72(1):59–66. doi: 10.1159/000234841. [DOI] [PubMed] [Google Scholar]
  4. Enander I., Ahlstedt S., Nygren H. Cyclophosphamide-mediated enhancement of delayed hypersensitivity reactions in the lung. Int Arch Allergy Appl Immunol. 1986;79(3):291–295. doi: 10.1159/000233989. [DOI] [PubMed] [Google Scholar]
  5. Enander I., Ahlstedt S., Nygren H. Mononuclear cells, mast cells and mucous cells as part of the delayed hypersensitivity response to aerosolized antigen in mice. Immunology. 1984 Apr;51(4):661–668. [PMC free article] [PubMed] [Google Scholar]
  6. Enander I., Ulfgren A. K., Nygren H., Holmdahl R., Klareskog L., Larsson P., Ahlstedt S. Regulation of the delayed hypersensitivity reaction in the lung reflected as mononuclear, mast cell and mucus cell appearance after T helper cell depletion and adoptive transfer. Int Arch Allergy Appl Immunol. 1987;82(3-4):361–363. doi: 10.1159/000234227. [DOI] [PubMed] [Google Scholar]
  7. Enander I., Ulfgren A., Nygren H., Larsson P., Holmdahl R., Klareskog L., Ahlstedt S. Regulation by T cells of delayed hypersensitivity reaction in mouse lung as reflected by mononuclear cells, mast cells and mucus-producing cells. Int Arch Allergy Appl Immunol. 1988;85(3):374–380. doi: 10.1159/000234535. [DOI] [PubMed] [Google Scholar]
  8. Galli S. J., Hammel I. Unequivocal delayed hypersensitivity in mast cell-deficient and beige mice. Science. 1984 Nov 9;226(4675):710–713. doi: 10.1126/science.6494907. [DOI] [PubMed] [Google Scholar]
  9. Ha T. Y., Reed N. D., Crowle P. K. Immune response potential of mast cell-deficient W/Wv mice. Int Arch Allergy Appl Immunol. 1986;80(1):85–94. doi: 10.1159/000234031. [DOI] [PubMed] [Google Scholar]
  10. Johnson K. J., Ward P. A. Acute immunologic pulmonary alveolitis. J Clin Invest. 1974 Aug;54(2):349–357. doi: 10.1172/JCI107770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kops S. K., Van Loveren H., Rosenstein R. W., Ptak W., Askenase P. W. Mast cell activation and vascular alterations in immediate hypersensitivity-like reactions induced by a T cell-derived antigen-binding factor. Lab Invest. 1984 Apr;50(4):421–434. [PubMed] [Google Scholar]
  12. Leysen J. E., Awouters F., Kennis L., Laduron P. M., Vandenberk J., Janssen P. A. Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci. 1981 Mar 2;28(9):1015–1022. doi: 10.1016/0024-3205(81)90747-5. [DOI] [PubMed] [Google Scholar]
  13. Mekori Y. A., Chang J. C., Wershil B. K., Galli S. J. Studies of the role of mast cells in contact sensitivity responses. Passive transfer of the reaction into mast cell-deficient mice locally reconstituted with cultured mast cells: effect of reserpine on transfer of the reaction with DNP-specific cloned T cells. Cell Immunol. 1987 Oct 1;109(1):39–52. doi: 10.1016/0008-8749(87)90290-5. [DOI] [PubMed] [Google Scholar]
  14. Mekori Y. A., Weitzman G. L., Galli S. J. Reevaluation of reserpine-induced suppression of contact sensitivity. Evidence that reserpine interferes with T lymphocyte function independently of an effect on mast cells. J Exp Med. 1985 Dec 1;162(6):1935–1953. doi: 10.1084/jem.162.6.1935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miyamoto T., Kabe J., Noda M., Kobayashi N., Miura K. Physiologic and pathologic respiratory changes in delayed type hypersensitivity reaction in guinea pigs. Am Rev Respir Dis. 1971 Apr;103(4):509–515. doi: 10.1164/arrd.1971.103.4.509. [DOI] [PubMed] [Google Scholar]
  16. Popa V., Teculescu D., Stănescu D., Gavrilescu N. Bronchial asthma and asthmatic bronchitis determined by simple chemicals. Dis Chest. 1969 Nov;56(5):395–402. doi: 10.1378/chest.56.5.395. [DOI] [PubMed] [Google Scholar]
  17. Ptak W., Bereta M., Ptak M., Askenase P. W. Isotype-like suppression of T cell-mediated immunity in vivo. I. Delayed-type hypersensitivity specificity of T cell suppression induced by antigen-binding T cell factors that initiate contact sensitivity. J Immunol. 1986 Mar 1;136(5):1554–1563. [PubMed] [Google Scholar]
  18. Thomas W. R., Schrader J. W. Delayed hypersensitivity in mast-cell-deficient mice. J Immunol. 1983 Jun;130(6):2565–2567. [PubMed] [Google Scholar]
  19. Van Loveren H., Askenase P. W. Delayed-type hypersensitivity is mediated by a sequence of two different T cell activities. J Immunol. 1984 Nov;133(5):2397–2401. [PubMed] [Google Scholar]
  20. Van Loveren H., Kraeuter-Kops S., Askenase P. W. Different mechanisms of release of vasoactive amines by mast cells occur in T cell-dependent compared to IgE-dependent cutaneous hypersensitivity responses. Eur J Immunol. 1984 Jan;14(1):40–47. doi: 10.1002/eji.1830140108. [DOI] [PubMed] [Google Scholar]

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