Abstract
The delayed-type hypersensitivity reaction (DHR) in human skin is prototypic for many inflammatory dermatoses. However the cellular events that precede gross lesion formation are unknown. In this study, inflammatory cell populations and adhesion molecule expression in early phases of DHR elicited by 2,4-dinitrochlorobenzene were evaluated. The first discernible event (at 1 hour) was mast cell degranulation, followed by induction of endothelial leukocyte adhesion molecule (ELAM-1) expression on dermal postcapillary venules at 2 hours. Endothelial leukocyte adhesion molecule expression peaked at 24 hours and declined by 48 hours. In contrast, endothelial expression of intercellular adhesion molecule-1 (ICAM-1) remained at constitutive levels. Intrafollicular T-cell migration occurred independent of ICAM-1 expression and commenced as early as 4 hours after challenge. Mature, activated CD4-positive lymphocytes that expressed a helper-inducer/memory phenotype predominated in early lesions. These results demonstrate in vivo that mast cell degranulation, ELAM-1 expression, and memory T-cell-follicular interactions are key events in subclinical evolutionary stages of cutaneous DHR.
Full text
PDF









Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
- Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
- Clement L. T., Yamashita N., Martin A. M. The functionally distinct subpopulations of human CD4+ helper/inducer T lymphocytes defined by anti-CD45R antibodies derive sequentially from a differentiation pathway that is regulated by activation-dependent post-thymic differentiation. J Immunol. 1988 Sep 1;141(5):1464–1470. [PubMed] [Google Scholar]
- Cotran R. S., Gimbrone M. A., Jr, Bevilacqua M. P., Mendrick D. L., Pober J. S. Induction and detection of a human endothelial activation antigen in vivo. J Exp Med. 1986 Aug 1;164(2):661–666. doi: 10.1084/jem.164.2.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cotran R. S. The endothelium and inflammation: new insights. Monogr Pathol. 1982;(23):18–37. [PubMed] [Google Scholar]
- Dustin M. L., Singer K. H., Tuck D. T., Springer T. A. Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1). J Exp Med. 1988 Apr 1;167(4):1323–1340. doi: 10.1084/jem.167.4.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dvorak A. M., Mihm M. C., Jr, Dvorak H. F. Morphology of delayed-type hypersensitivity reactions in man. II. Ultrastructural alterations affecting the microvasculature and the tissue mast cells. Lab Invest. 1976 Feb;34(2):179–191. [PubMed] [Google Scholar]
- Griffiths C. E., Voorhees J. J., Nickoloff B. J. Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: modulation by recombinant gamma interferon and tumor necrosis factor. J Am Acad Dermatol. 1989 Apr;20(4):617–629. doi: 10.1016/s0190-9622(89)70073-6. [DOI] [PubMed] [Google Scholar]
- Irani A. M., Bradford T. R., Kepley C. L., Schechter N. M., Schwartz L. B. Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies. J Histochem Cytochem. 1989 Oct;37(10):1509–1515. doi: 10.1177/37.10.2674273. [DOI] [PubMed] [Google Scholar]
- Klein L. M., Lavker R. M., Matis W. L., Murphy G. F. Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8972–8976. doi: 10.1073/pnas.86.22.8972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kupper T. S. The activated keratinocyte: a model for inducible cytokine production by non-bone marrow-derived cells in cutaneous inflammatory and immune responses. J Invest Dermatol. 1990 Jun;94(6 Suppl):146S–150S. doi: 10.1111/1523-1747.ep12876130. [DOI] [PubMed] [Google Scholar]
- Lewis R. E., Buchsbaum M., Whitaker D., Murphy G. F. Intercellular adhesion molecule expression in the evolving human cutaneous delayed hypersensitivity reaction. J Invest Dermatol. 1989 Nov;93(5):672–677. doi: 10.1111/1523-1747.ep12319838. [DOI] [PubMed] [Google Scholar]
- Lisby S., Ralfkiaer E., Rothlein R., Vejlsgaard G. L. Intercellular adhesion molecule-I (ICAM-I) expression correlated to inflammation. Br J Dermatol. 1989 Apr;120(4):479–484. doi: 10.1111/j.1365-2133.1989.tb01320.x. [DOI] [PubMed] [Google Scholar]
- Matis W. L., Lavker R. M., Murphy G. F. Substance P induces the expression of an endothelial-leukocyte adhesion molecule by microvascular endothelium. J Invest Dermatol. 1990 Apr;94(4):492–495. doi: 10.1111/1523-1747.ep12874665. [DOI] [PubMed] [Google Scholar]
- Merkenschlager M., Terry L., Edwards R., Beverley P. C. Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation. Eur J Immunol. 1988 Nov;18(11):1653–1661. doi: 10.1002/eji.1830181102. [DOI] [PubMed] [Google Scholar]
- Messadi D. V., Pober J. S., Fiers W., Gimbrone M. A., Jr, Murphy G. F. Induction of an activation antigen on postcapillary venular endothelium in human skin organ culture. J Immunol. 1987 Sep 1;139(5):1557–1562. [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Boyd A. W., Hagan M., Brown H. M., Kornacki M. M., Schlossman S. F. The isolation and characterization of the human helper inducer T cell subset. J Immunol. 1985 Jun;134(6):3762–3769. [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
- Nickoloff B. J., Griffiths C. E. T lymphocytes and monocytes bind to keratinocytes in frozen sections of biopsy specimens of normal skin treated with gamma interferon. J Am Acad Dermatol. 1989 May;20(5 Pt 1):736–743. doi: 10.1016/s0190-9622(89)70083-9. [DOI] [PubMed] [Google Scholar]
- Nickoloff B. J. Role of interferon-gamma in cutaneous trafficking of lymphocytes with emphasis on molecular and cellular adhesion events. Arch Dermatol. 1988 Dec;124(12):1835–1843. [PubMed] [Google Scholar]
- Osborn L., Hession C., Tizard R., Vassallo C., Luhowskyj S., Chi-Rosso G., Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. doi: 10.1016/0092-8674(89)90775-7. [DOI] [PubMed] [Google Scholar]
- Pitzalis C., Kingsley G., Haskard D., Panayi G. The preferential accumulation of helper-inducer T lymphocytes in inflammatory lesions: evidence for regulation by selective endothelial and homotypic adhesion. Eur J Immunol. 1988 Sep;18(9):1397–1404. doi: 10.1002/eji.1830180915. [DOI] [PubMed] [Google Scholar]
- Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
- Poulter L. W., Seymour G. J., Duke O., Janossy G., Panayi G. Immunohistological analysis of delayed-type hypersensitivity in man. Cell Immunol. 1982 Dec;74(2):358–369. doi: 10.1016/0008-8749(82)90036-3. [DOI] [PubMed] [Google Scholar]
- Sanders M. E., Makgoba M. W., Sharrow S. O., Stephany D., Springer T. A., Young H. A., Shaw S. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol. 1988 Mar 1;140(5):1401–1407. [PubMed] [Google Scholar]
- Smolle J. Mononuclear cell patterns in the skin. An immunohistological and morphometrical analysis. Am J Dermatopathol. 1988 Feb;10(1):36–46. doi: 10.1097/00000372-198802000-00005. [DOI] [PubMed] [Google Scholar]
- Staunton D. E., Dustin M. L., Springer T. A. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature. 1989 May 4;339(6219):61–64. doi: 10.1038/339061a0. [DOI] [PubMed] [Google Scholar]
- Tharp M. D., Kasper C., Thiele D., Charley M. R., Kennerly D. A., Sullivan T. J. Studies of connective tissue mast cell-mediated cytotoxicity. J Invest Dermatol. 1989 Sep;93(3):423–428. [PubMed] [Google Scholar]
- Tigelaar R. E., Lewis J. M., Bergstresser P. R. TCR gamma/delta+ dendritic epidermal T cells as constituents of skin-associated lymphoid tissue. J Invest Dermatol. 1990 Jun;94(6 Suppl):58S–63S. doi: 10.1111/1523-1747.ep12875138. [DOI] [PubMed] [Google Scholar]
- Walsh L. J., Lavker R. M., Murphy G. F. Determinants of immune cell trafficking in the skin. Lab Invest. 1990 Nov;63(5):592–600. [PubMed] [Google Scholar]
- Willms-Kretschmer K., Flax M. H., Cotran R. S. The fine structure of the vascular response in hapten-specific delayed hypersensitivity and contact dermatitis. Lab Invest. 1967 Sep;17(3):334–349. [PubMed] [Google Scholar]
- Young J. D., Liu C. C., Butler G., Cohn Z. A., Galli S. J. Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9175–9179. doi: 10.1073/pnas.84.24.9175. [DOI] [PMC free article] [PubMed] [Google Scholar]