Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Apr 1;167(4):1323–1340. doi: 10.1084/jem.167.4.1323

Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1)

PMCID: PMC2188928  PMID: 3128630

Abstract

The cell surface expression and function of the LFA-1 ligand, intercellular adhesion molecule 1 (ICAM-1), on epidermal keratinocytes (EK) was studied. ICAM-1 expression on the surface of cultured EK was either absent or weak, but was induced by treating EK with rIFN-gamma or TNF for 4-48 h. IFN-gamma and TNF were synergistic. IFN-gamma treatment increased T lymphoblast adhesion from less than 2% to 20-40%, with a concentration dependence similar to that seen for ICAM-1 induction. All of the adhesion to EK was inhibited by LFA-1 and ICAM-1 mAbs, but not by HLA-DR, CD2, or LFA-3 mAbs. There was no difference in the level of T lymphoblast adhesion to IFN-gamma-treated allogeneic or autologous EK. ICAM-1 purified from the HeLa epithelioid cell line and reconstituted into planar membranes also supported efficient adhesion of T lymphoblasts that was blocked by LFA-1 mAb bound to the T lymphoblasts or ICAM-1 mAb bound to the planar membranes. T lymphoblasts adherent to EK or ICAM-1 planar membranes were isolated by panning, and surface markers were analyzed by immunofluorescence flow cytometry. The adherent T cells were a phenotypically skewed subpopulation. They were enriched for CD8+ cells and expressed 1.5-2.5- fold higher LFA-1 and CD2 compared with the unseparated population.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Anderson D. C., Springer T. A. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175–194. doi: 10.1146/annurev.me.38.020187.001135. [DOI] [PubMed] [Google Scholar]
  2. Barclay A. N., Mason D. W. Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli. J Exp Med. 1982 Dec 1;156(6):1665–1676. doi: 10.1084/jem.156.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  4. Basham T. Y., Nickoloff B. J., Merigan T. C., Morhenn V. B. Recombinant gamma interferon induces HLA-DR expression on cultured human keratinocytes. J Invest Dermatol. 1984 Aug;83(2):88–90. doi: 10.1111/1523-1747.ep12262597. [DOI] [PubMed] [Google Scholar]
  5. Bjerke J. R. Subpopulations of mononuclear cells in lesions of psoriasis, lichen planus and discoid lupus erythematosus studied using monoclonal antibodies. Acta Derm Venereol. 1982;62(6):477–483. [PubMed] [Google Scholar]
  6. Brian A. A., McConnell H. M. Allogeneic stimulation of cytotoxic T cells by supported planar membranes. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6159–6163. doi: 10.1073/pnas.81.19.6159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Broder S., Edelson R. L., Lutzner M. A., Nelson D. L., MacDermott R. P., Durm M. E., Goldman C. K., Meade B. D., Waldmann T. A. The Sézary syndrome: a malignant proliferation of helper T cells. J Clin Invest. 1976 Dec;58(6):1297–1306. doi: 10.1172/JCI108585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chang T. W., Celis E., Eisen H. N., Solomon F. Crawling movements of lymphocytes on and beneath fibroblasts in culture. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2917–2921. doi: 10.1073/pnas.76.6.2917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  10. Dustin M. L., Sanders M. E., Shaw S., Springer T. A. Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. J Exp Med. 1987 Mar 1;165(3):677–692. doi: 10.1084/jem.165.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Edelson R. L., Fink J. M. The immunologic function of skin. Sci Am. 1985 Jun;252(6):46–53. doi: 10.1038/scientificamerican0685-46. [DOI] [PubMed] [Google Scholar]
  12. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  13. Galfrè G., Milstein C. Preparation of monoclonal antibodies: strategies and procedures. Methods Enzymol. 1981;73(Pt B):3–46. doi: 10.1016/0076-6879(81)73054-4. [DOI] [PubMed] [Google Scholar]
  14. Gay D., Coeshott C., Golde W., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells. IX. Role of accessory molecules in recognition of antigen plus isolated IA. J Immunol. 1986 Mar 15;136(6):2026–2032. [PubMed] [Google Scholar]
  15. Gielkens A. L., Van Zaane D., Bloemers H. P., Bloemendal H. Synthesis of Rauscher murine leukemia virus-specific polypeptides in vitro. Proc Natl Acad Sci U S A. 1976 Feb;73(2):356–360. doi: 10.1073/pnas.73.2.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hashimoto K., Shafran K. M., Webber P. S., Lazarus G. S., Singer K. H. Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation. J Exp Med. 1983 Jan 1;157(1):259–272. doi: 10.1084/jem.157.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haskard D., Cavender D., Beatty P., Springer T., Ziff M. T lymphocyte adhesion to endothelial cells: mechanisms demonstrated by anti-LFA-1 monoclonal antibodies. J Immunol. 1986 Nov 1;137(9):2901–2906. [PubMed] [Google Scholar]
  18. Herrmann F., Dörken B., Ludwig W. D., Schwarting R. A comparison of membrane marker phenotypes in hairy-cell leukemia and phorbol-ester induced B-cll cells using monoclonal antibodies. Leuk Res. 1985;9(5):529–536. doi: 10.1016/0145-2126(85)90132-8. [DOI] [PubMed] [Google Scholar]
  19. Krensky A. M., Robbins E., Springer T. A., Burakoff S. J. LFA-1, LFA-2, and LFA-3 antigens are involved in CTL-target conjugation. J Immunol. 1984 May;132(5):2180–2182. [PubMed] [Google Scholar]
  20. Krensky A. M., Sanchez-Madrid F., Robbins E., Nagy J. A., Springer T. A., Burakoff S. J. The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: cell surface antigens associated with CTL-target interactions. J Immunol. 1983 Aug;131(2):611–616. [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. Lampert I. A., Janossy G., Suitters A. J., Bofill M., Palmer S., Gordon-Smith E., Prentice H. G., Thomas J. A. Immunological analysis of the skin in graft versus host disease. Clin Exp Immunol. 1982 Oct;50(1):123–131. [PMC free article] [PubMed] [Google Scholar]
  23. Lampert I. A., Suitters A. J., Chisholm P. M. Expression of Ia antigen on epidermal keratinocytes in graft-versus-host disease. Nature. 1981 Sep 10;293(5828):149–150. doi: 10.1038/293149a0. [DOI] [PubMed] [Google Scholar]
  24. Luger T. A., Stadler B. M., Luger B. M., Mathieson B. J., Mage M., Schmidt J. A., Oppenheim J. J. Murine epidermal cell-derived thymocyte-activating factor resembles murine interleukin 1. J Immunol. 1982 May;128(5):2147–2152. [PubMed] [Google Scholar]
  25. Lutzner M., Edelson R., Schein P., Green I., Kirkpatrick C., Ahmed A. Cutaneous T-cell lymphomas: the Sézary syndrome, mycosis fungoides, and related disorders. Ann Intern Med. 1975 Oct;83(4):534–552. doi: 10.7326/0003-4819-83-4-534. [DOI] [PubMed] [Google Scholar]
  26. March S. C., Parikh I., Cuatrecasas P. A simplified method for cyanogen bromide activation of agarose for affinity chromatography. Anal Biochem. 1974 Jul;60(1):149–152. doi: 10.1016/0003-2697(74)90139-0. [DOI] [PubMed] [Google Scholar]
  27. Marlin S. D., Springer T. A. Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell. 1987 Dec 4;51(5):813–819. doi: 10.1016/0092-8674(87)90104-8. [DOI] [PubMed] [Google Scholar]
  28. Mason D. W., Dallman M., Barclay A. N. Graft-versus-host disease induces expression of Ia antigen in rat epidermal cells and gut epithelium. Nature. 1981 Sep 10;293(5828):150–151. doi: 10.1038/293150a0. [DOI] [PubMed] [Google Scholar]
  29. McGregor D. D., Logie P. S. The mediator of cellular immunity. VII. Localization of sensitized lymphocytes in inflammatory exudates. J Exp Med. 1974 Jun 1;139(6):1415–1430. doi: 10.1084/jem.139.6.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Miossec P., Yu C. L., Ziff M. Lymphocyte chemotactic activity of human interleukin 1. J Immunol. 1984 Oct;133(4):2007–2011. [PubMed] [Google Scholar]
  31. Morrissey J. H. Silver stain for proteins in polyacrylamide gels: a modified procedure with enhanced uniform sensitivity. Anal Biochem. 1981 Nov 1;117(2):307–310. doi: 10.1016/0003-2697(81)90783-1. [DOI] [PubMed] [Google Scholar]
  32. Nickoloff B. J., Lewinsohn D. M., Butcher E. C. Enhanced binding of peripheral blood mononuclear leukocytes to gamma-interferon-treated cultured keratinocytes. Am J Dermatopathol. 1987 Oct;9(5):413–418. doi: 10.1097/00000372-198710000-00007. [DOI] [PubMed] [Google Scholar]
  33. Patarroyo M., Beatty P. G., Fabre J. W., Gahmberg C. G. Identification of a cell surface protein complex mediating phorbol ester-induced adhesion (binding) among human mononuclear leukocytes. Scand J Immunol. 1985 Aug;22(2):171–182. doi: 10.1111/j.1365-3083.1985.tb01869.x. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Roos E., Roossien F. F. Involvement of leukocyte function-associated antigen-1 (LFA-1) in the invasion of hepatocyte cultures by lymphoma and T-cell hybridoma cells. J Cell Biol. 1987 Jul;105(1):553–559. doi: 10.1083/jcb.105.1.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rothlein R., Dustin M. L., Marlin S. D., Springer T. A. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986 Aug 15;137(4):1270–1274. [PubMed] [Google Scholar]
  38. Rothlein R., Springer T. A. The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester. J Exp Med. 1986 May 1;163(5):1132–1149. doi: 10.1084/jem.163.5.1132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sanchez-Madrid F., Krensky A. M., Ware C. F., Robbins E., Strominger J. L., Burakoff S. J., Springer T. A. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7489–7493. doi: 10.1073/pnas.79.23.7489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sauder D. N., Carter C. S., Katz S. I., Oppenheim J. J. Epidermal cell production of thymocyte activating factor (ETAF). J Invest Dermatol. 1982 Jul;79(1):34–39. doi: 10.1111/1523-1747.ep12510569. [DOI] [PubMed] [Google Scholar]
  41. Scheynius A., Klareskog L., Forsum U. In situ identification of T lymphocyte subsets and HLA-DR expressing cells in the human skin tuberculin reaction. Clin Exp Immunol. 1982 Aug;49(2):325–330. [PMC free article] [PubMed] [Google Scholar]
  42. Shaw S., Luce G. E. The lymphocyte function-associated antigen (LFA)-1 and CD2/LFA-3 pathways of antigen-independent human T cell adhesion. J Immunol. 1987 Aug 15;139(4):1037–1045. [PubMed] [Google Scholar]
  43. Springer T. A., Dustin M. L., Kishimoto T. K., Marlin S. D. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol. 1987;5:223–252. doi: 10.1146/annurev.iy.05.040187.001255. [DOI] [PubMed] [Google Scholar]
  44. Streilein J. W. Circuits and signals of the skin-associated lymphoid tissues (SALT). J Invest Dermatol. 1985 Jul;85(1 Suppl):10s–13s. doi: 10.1111/1523-1747.ep12275413. [DOI] [PubMed] [Google Scholar]
  45. Streilein J. W. Lymphocyte traffic, T-cell malignancies and the skin. J Invest Dermatol. 1978 Sep;71(3):167–171. doi: 10.1111/1523-1747.ep12547071. [DOI] [PubMed] [Google Scholar]
  46. Suitters A. J., Lampert I. A. Expression of Ia antigen on epidermal keratinocytes is a consequence of cellular immunity. Br J Exp Pathol. 1982 Apr;63(2):207–213. [PMC free article] [PubMed] [Google Scholar]
  47. Tjernlund U. M. Epidermal expression of HLA-DR antigens in mycosis fungoides. Arch Dermatol Res. 1978 Feb 15;261(1):81–86. doi: 10.1007/BF00455380. [DOI] [PubMed] [Google Scholar]
  48. Tjernlund U. M. Ia-like antigens in lichen planus. Acta Derm Venereol. 1980;60(4):309–314. doi: 10.2340/0001555560309314. [DOI] [PubMed] [Google Scholar]
  49. Vollger L. W., Tuck D. T., Springer T. A., Haynes B. F., Singer K. H. Thymocyte binding to human thymic epithelial cells is inhibited by monoclonal antibodies to CD-2 and LFA-3 antigens. J Immunol. 1987 Jan 15;138(2):358–363. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES