Early molecular events in the induction phase of contact sensitivity (original) (raw)

Abstract

To assess changes in epidermis-derived cytokine mRNA levels early in the afferent phase of allergic contact sensitivity, total epidermal mRNA was analyzed at various times after painting skin with haptens. We used a sensitive reverse transcriptase-polymerase chain reaction technique to quantitatively compare the regulation patterns of the following mRNAs: class II major histocompatibility complex I-A alpha, tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1 alpha, IL-1 beta, interferon (IFN) gamma, granulocyte/macrophage colony-stimulating factor, IFN-induced protein 10, and macrophage inflammatory protein 2. Enhanced Langerhans cell-derived IL-1 beta mRNA signals were detected as early as 15 min after skin painting with allergens. TNF-alpha, IFN-gamma, and granulocyte/macrophage colony-stimulating factor mRNAs were found to be upregulated after application of allergens, irritant, and tolerogens, but class II major histocompatibility complex I-A alpha, IL-1 alpha, IL-1 beta, IFN-induced protein 10, and macrophage inflammatory protein 2 mRNAs were upregulated only after allergen painting. Depletion of specific cell populations demonstrated that Langerhans cells were the primary source of the IL-1 beta and class II major histocompatibility complex I-A alpha mRNAs, keratinocytes were the primary source of TNF-alpha, IL-1 alpha, IFN-induced protein 10, and macrophage inflammatory protein 2, and infiltrating T lymphocytes were the source of IFN-gamma. Relevance of the molecular findings was demonstrated by the identification of biologically active IL-1 alpha and immunoreactive TNF-alpha in culture supernatants. These studies demonstrate that Langerhans cell-derived and certain keratinocyte-derived cytokine mRNAs are selectively upregulated by allergens in the very early afferent phase of contact sensitivity.

1398

Images in this article

Selected References

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

  1. Aiba S., Katz S. I. Phenotypic and functional characteristics of in vivo-activated Langerhans cells. J Immunol. 1990 Nov 1;145(9):2791–2796. [PubMed] [Google Scholar]
  2. Baadsgaard O., Tong P., Elder J. T., Hansen E. R., Ho V., Hammerberg C., Lange-Vejlsgaard G., Fox D. A., Fisher G., Chan L. S. UM4D4+ (CDw60) T cells are compartmentalized into psoriatic skin and release lymphokines that induce a keratinocyte phenotype expressed in psoriatic lesions. J Invest Dermatol. 1990 Sep;95(3):275–282. doi: 10.1111/1523-1747.ep12484908. [DOI] [PubMed] [Google Scholar]
  3. Bhattacharya A., Dorf M. E., Springer T. A. A shared alloantigenic determinant on Ia antigens encoded by the I-A and I-E subregions: evidence for I region gene duplication. J Immunol. 1981 Dec;127(6):2488–2495. [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Gaspari A. A., Jenkins M. K., Katz S. I. Class II MHC-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific Th1 clones. J Immunol. 1988 Oct 1;141(7):2216–2220. [PubMed] [Google Scholar]
  6. Gearing A. J., Bird C. R., Bristow A., Poole S., Thorpe R. A simple sensitive bioassay for interleukin-1 which is unresponsive to 10(3) U/ml of interleukin-2. J Immunol Methods. 1987 May 4;99(1):7–11. doi: 10.1016/0022-1759(87)90025-1. [DOI] [PubMed] [Google Scholar]
  7. Hogquist K. A., Nett M. A., Sheehan K. C., Pendleton K. D., Schreiber R. D., Chaplin D. D. Generation of monoclonal antibodies to murine IL-1 beta and demonstration of IL-1 in vivo. J Immunol. 1991 Mar 1;146(5):1534–1540. [PubMed] [Google Scholar]
  8. Kaplan G., Luster A. D., Hancock G., Cohn Z. A. The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin. J Exp Med. 1987 Oct 1;166(4):1098–1108. doi: 10.1084/jem.166.4.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Larsen C. P., Steinman R. M., Witmer-Pack M., Hankins D. F., Morris P. J., Austyn J. M. Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med. 1990 Nov 1;172(5):1483–1493. doi: 10.1084/jem.172.5.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Luster A. D., Ravetch J. V. Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med. 1987 Oct 1;166(4):1084–1097. doi: 10.1084/jem.166.4.1084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Macatonia S. E., Edwards A. J., Knight S. C. Dendritic cells and the initiation of contact sensitivity to fluorescein isothiocyanate. Immunology. 1986 Dec;59(4):509–514. [PMC free article] [PubMed] [Google Scholar]
  12. Macatonia S. E., Knight S. C., Edwards A. J., Griffiths S., Fryer P. Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J Exp Med. 1987 Dec 1;166(6):1654–1667. doi: 10.1084/jem.166.6.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Milstone L. M. Effector functions of epidermal keratinocytes. Ann N Y Acad Sci. 1988;548:1–3. doi: 10.1111/j.1749-6632.1988.tb18787.x. [DOI] [PubMed] [Google Scholar]
  14. Ohmori Y., Hamilton T. A. A macrophage LPS-inducible early gene encodes the murine homologue of IP-10. Biochem Biophys Res Commun. 1990 May 16;168(3):1261–1267. doi: 10.1016/0006-291x(90)91164-n. [DOI] [PubMed] [Google Scholar]
  15. Piguet P. F., Grau G. E., Hauser C., Vassalli P. Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. J Exp Med. 1991 Mar 1;173(3):673–679. doi: 10.1084/jem.173.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
  17. Sauder D. N., Dinarello C. A., Morhenn V. B. Langerhans cell production of interleukin-1. J Invest Dermatol. 1984 Jun;82(6):605–607. doi: 10.1111/1523-1747.ep12261439. [DOI] [PubMed] [Google Scholar]
  18. Sherry B., Cerami A. Small cytokine superfamily. Curr Opin Immunol. 1991 Feb;3(1):56–60. doi: 10.1016/0952-7915(91)90077-e. [DOI] [PubMed] [Google Scholar]
  19. Shimada S., Katz S. I. TNP-specific Lyt-2+ cytolytic T cell clones preferentially respond to TNP-conjugated epidermal cells. J Immunol. 1985 Sep;135(3):1558–1563. [PubMed] [Google Scholar]
  20. Silberberg-Sinakin I., Thorbecke G. J., Baer R. L., Rosenthal S. A., Berezowsky V. Antigen-bearing langerhans cells in skin, dermal lymphatics and in lymph nodes. Cell Immunol. 1976 Aug;25(2):137–151. doi: 10.1016/0008-8749(76)90105-2. [DOI] [PubMed] [Google Scholar]
  21. Smith W. B., Gamble J. R., Clark-Lewis I., Vadas M. A. Interleukin-8 induces neutrophil transendothelial migration. Immunology. 1991 Jan;72(1):65–72. [PMC free article] [PubMed] [Google Scholar]
  22. Tekamp-Olson P., Gallegos C., Bauer D., McClain J., Sherry B., Fabre M., van Deventer S., Cerami A. Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. J Exp Med. 1990 Sep 1;172(3):911–919. doi: 10.1084/jem.172.3.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Van Damme J., Opdenakker G. Interaction of interferons with skin reactive cytokines: from interleukin-1 to interleukin-8. J Invest Dermatol. 1990 Dec;95(6 Suppl):90S–93S. doi: 10.1111/1523-1747.ep12874825. [DOI] [PubMed] [Google Scholar]
  24. Witsell A. L., Schook L. B. Clonal analysis of gene expression by PCR. Biotechniques. 1990 Sep;9(3):318–322. [PubMed] [Google Scholar]
  25. Wolpe S. D., Cerami A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 1989 Dec;3(14):2565–2573. doi: 10.1096/fasebj.3.14.2687068. [DOI] [PubMed] [Google Scholar]
  26. Wolpe S. D., Sherry B., Juers D., Davatelis G., Yurt R. W., Cerami A. Identification and characterization of macrophage inflammatory protein 2. Proc Natl Acad Sci U S A. 1989 Jan;86(2):612–616. doi: 10.1073/pnas.86.2.612. [DOI] [PMC free article] [PubMed] [Google Scholar]