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. 1986 May;77(5):1596–1605. doi: 10.1172/JCI112475

Mechanisms of lymphocyte adhesion to human vascular endothelial cells in culture. T lymphocyte adhesion to endothelial cells through endothelial HLA-DR antigens induced by gamma interferon.

J Masuyama, N Minato, S Kano
PMCID: PMC424563  PMID: 3084562

Abstract

The effects of interferons (IFNs) on lymphocyte adhesion to cultured human vascular endothelial cells (EC) were investigated using an in vitro assay. Endothelial cells obtained from umbilical vein were first cultured at a low density with a conditioned medium (CM) from 12-O-tetra decanoylphorbol 13-acetate-concanavalin A (TPA-Con A) stimulated human peripheral blood lymphocytes (PBL), or with recombinant (r) gamma interferon (IFN-gamma) or r alpha interferon (IFN-alpha), and then were incubated with freshly isolated PBL. Natural IFN-gamma in the TPA-Con A CM and rIFN-gamma (12.5-500 U/ml) induced major histocompatibility complex-class II antigens (HLA-DR, HLA-DP, and HLA-DQ) and significant lymphocyte adhesion to the EC, whereas rIFN-alpha did not. The lymphocyte adhesion to the EC and the expression of DR antigens on the EC were well correlated in terms of both kinetics and the dose-response pattern of rIFN-gamma. When EC expressing I region associated (Ia) antigen were preincubated with monoclonal anti-DR antibody before the addition of lymphocytes, the lymphocyte adhesion was significantly inhibited in both allogeneic and syngeneic combinations, whereas anti-HLA-DP, anti-HLA-DQ, and anti-HLA-ABC antibodies did not inhibit the binding at all. Cell fractionation experiments indicated that the majority of lymphocytes adhering to Ia-expressed EC were Leu-3+ T cells, whose binding was again almost completely inhibited by anti-DR antibody. Moreover, anti-Leu-3a, but not anti-Leu-2a, antibody effectively inhibited the T cell adhesion to the EC. These results strongly suggest that the interaction of the Leu-3(T4) receptor of T cells with IFN-gamma-induced DR antigens on EC plays a central role in the selective adhesion of Leu-3+ T cell to EC.

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Selected References

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  1. Aström K. E., Webster H. D., Arnason B. G. The initial lesion in experimental allergic neuritis. A phase and electron microscopic study. J Exp Med. 1968 Sep 1;128(3):469–495. doi: 10.1084/jem.128.3.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhan A. K., Mihm M. C., Jr, Dvorak H. F. T cell subsets in allograft rejection. In situ characterization of T cell subsets in human skin allografts by the use of monoclonal antibodies. J Immunol. 1982 Oct;129(4):1578–1583. [PubMed] [Google Scholar]
  4. Biddison W. E., Rao P. E., Talle M. A., Goldstein G., Shaw S. Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of cytotoxic T lymphocytes specific for SB antigens. J Exp Med. 1982 Oct 1;156(4):1065–1076. doi: 10.1084/jem.156.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bottomly K., Jones B., Kaye J., Jones F., 3rd Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells. J Exp Med. 1983 Aug 1;158(2):265–279. doi: 10.1084/jem.158.2.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Butcher E. C., Scollay R. G., Weissman I. L. Organ specificity of lymphocyte migration: mediation by highly selective lymphocyte interaction with organ-specific determinants on high endothelial venules. Eur J Immunol. 1980 Jul;10(7):556–561. doi: 10.1002/eji.1830100713. [DOI] [PubMed] [Google Scholar]
  7. Chin Y. H., Carey G. D., Woodruff J. J. Lymphocyte recognition of lymph node high endothelium. IV. Cell surface structures mediating entry into lymph nodes. J Immunol. 1982 Nov;129(5):1911–1915. [PubMed] [Google Scholar]
  8. Chin Y. H., Carey G. D., Woodruff J. J. Lymphocyte recognition of lymph node high endothelium. V. Isolation of adhesion molecules from lysates of rat lymphocytes. J Immunol. 1983 Sep;131(3):1368–1374. [PubMed] [Google Scholar]
  9. Collins T., Korman A. J., Wake C. T., Boss J. M., Kappes D. J., Fiers W., Ault K. A., Gimbrone M. A., Jr, Strominger J. L., Pober J. S. Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4917–4921. doi: 10.1073/pnas.81.15.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Collins T., Krensky A. M., Clayberger C., Fiers W., Gimbrone M. A., Jr, Burakoff S. J., Pober J. S. Human cytolytic T lymphocyte interactions with vascular endothelium and fibroblasts: role of effector and target cell molecules. J Immunol. 1984 Oct;133(4):1878–1884. [PubMed] [Google Scholar]
  11. Corte G., Damiani G., Calabi F., Fabbi M., Bargellesi A. Analysis of HLA-DR polymorphism by two-dimensional peptide mapping. Proc Natl Acad Sci U S A. 1981 Jan;78(1):534–538. doi: 10.1073/pnas.78.1.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  13. Ford W. L., Sedgley M., Sparshott S. M., Smith M. E. The migration of lymphocytes across specialized vascular endothelium. II. The contrasting consequences of treating lymphocytes with tryspin or neuraminidase. Cell Tissue Kinet. 1976 Jul;9(4):351–361. [PubMed] [Google Scholar]
  14. Gallatin W. M., Weissman I. L., Butcher E. C. A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature. 1983 Jul 7;304(5921):30–34. doi: 10.1038/304030a0. [DOI] [PubMed] [Google Scholar]
  15. Hirschberg H., Bergh O. J., Thorsby E. Antigen-presenting properties of human vascular endothelial cells. J Exp Med. 1980 Aug 1;152(2 Pt 2):249s–255s. [PubMed] [Google Scholar]
  16. Hoover R. L., Briggs R. T., Karnovsky M. J. The adhesive interaction between polymorphonuclear leukocytes and endothelial cells in vitro. Cell. 1978 Jun;14(2):423–428. doi: 10.1016/0092-8674(78)90127-7. [DOI] [PubMed] [Google Scholar]
  17. Issekutz T. B., Chin W., Hay J. B. Lymphocyte traffic through granulomas: differences in the recovery of indium-111-labeled lymphocytes in afferent and efferent lymph. Cell Immunol. 1980 Aug 15;54(1):79–86. doi: 10.1016/0008-8749(80)90191-4. [DOI] [PubMed] [Google Scholar]
  18. Issekutz T. B., Chin W., Hay J. B. The characterization of lymphocytes migrating through chronically inflamed tissues. Immunology. 1982 May;46(1):59–66. [PMC free article] [PubMed] [Google Scholar]
  19. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Janeway C. A., Jr, Bottomly K., Horowitz J., Kaye J., Jones B., Tite J. Modes of cell:cell communication in the immune system. J Immunol. 1985 Aug;135(2 Suppl):739s–742s. [PubMed] [Google Scholar]
  21. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  22. Krensky A. M., Clayberger C., Reiss C. S., Strominger J. L., Burakoff S. J. Specificity of OKT4+ cytotoxic T lymphocyte clones. J Immunol. 1982 Nov;129(5):2001–2003. [PubMed] [Google Scholar]
  23. Ly I. A., Mishell R. I. Separation of mouse spleen cells by passage through columns of sephadex G-10. J Immunol Methods. 1974 Aug;5(3):239–247. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
  24. Mentzer S. J., Gromkowski S. H., Krensky A. M., Burakoff S. J., Martz E. LFA-1 membrane molecule in the regulation of homotypic adhesions of human B lymphocytes. J Immunol. 1985 Jul;135(1):9–11. [PubMed] [Google Scholar]
  25. Meuer S. C., Fitzgerald K. A., Hussey R. E., Hodgdon J. C., Schlossman S. F., Reinherz E. L. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med. 1983 Feb 1;157(2):705–719. doi: 10.1084/jem.157.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Meuer S. C., Schlossman S. F., Reinherz E. L. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395–4399. doi: 10.1073/pnas.79.14.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Minato N., Takeda A., Kano S., Takaku F. Studies of the function of natural killer-interferon system in patients with Sjögren syndrome. J Clin Invest. 1982 Mar;69(3):581–588. doi: 10.1172/JCI110484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Montesano R., Mossaz A., Ryser J. E., Orci L., Vassalli P. Leukocyte interleukins induce cultured endothelial cells to produce a highly organized, glycosaminoglycan-rich pericellular matrix. J Cell Biol. 1984 Nov;99(5):1706–1715. doi: 10.1083/jcb.99.5.1706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nunez G., Ball E. J., Stastny P. Accessory cell function of human endothelial cells. I. A subpopulation of Ia positive cells is required for antigen presentation. J Immunol. 1983 Aug;131(2):666–673. [PubMed] [Google Scholar]
  30. Pedersen N. C., Morris B. The role of the lymphatic system in the rejection of homografts: a study of lymph from renal transplants. J Exp Med. 1970 May 1;131(5):936–969. doi: 10.1084/jem.131.5.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pober J. S., Collins T., Gimbrone M. A., Jr, Cotran R. S., Gitlin J. D., Fiers W., Clayberger C., Krensky A. M., Burakoff S. J., Reiss C. S. Lymphocytes recognize human vascular endothelial and dermal fibroblast Ia antigens induced by recombinant immune interferon. Nature. 1983 Oct 20;305(5936):726–729. doi: 10.1038/305726a0. [DOI] [PubMed] [Google Scholar]
  32. Pober J. S., Gimbrone M. A., Jr, Cotran R. S., Reiss C. S., Burakoff S. J., Fiers W., Ault K. A. Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon. J Exp Med. 1983 Apr 1;157(4):1339–1353. doi: 10.1084/jem.157.4.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Smith J. B., McIntosh G. H., Morris B. The migration of cells through chronically inflamed tissues. J Pathol. 1970 Jan;100(1):21–29. doi: 10.1002/path.1711000104. [DOI] [PubMed] [Google Scholar]
  34. Sobel R. A., Blanchette B. W., Bhan A. K., Colvin R. B. The immunopathology of experimental allergic encephalomyelitis. II. Endothelial cell Ia increases prior to inflammatory cell infiltration. J Immunol. 1984 May;132(5):2402–2407. [PubMed] [Google Scholar]
  35. Sobel R. A., Blanchette B. W., Colvin R. B. Pre-inflammatory expression of fibronectin (Fn) and Ia in acute experimental allergic encephalomyelitis (EAE): modulation of endothelial cells (EC) in the immune response detected by quantitative immunoperoxidase studies using monoclonal antibodies (MAb). Prog Clin Biol Res. 1984;146:81–86. [PubMed] [Google Scholar]
  36. Steinman L., Solomon D., Lim M., Zamvil S., Sriram S. Prevention of experimental allergic encephalitis with in vivo administration of anti I-A antibody. Decreased accumulation of radiolabelled lymph node cells in the central nervous system. J Neuroimmunol. 1983 Aug;5(1):91–97. doi: 10.1016/0165-5728(83)90029-2. [DOI] [PubMed] [Google Scholar]
  37. Stoolman L. M., Rosen S. D. Possible role for cell-surface carbohydrate-binding molecules in lymphocyte recirculation. J Cell Biol. 1983 Mar;96(3):722–729. doi: 10.1083/jcb.96.3.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sumiya M., Kano S., Oshimi K., Gonda N., Takaku F. Stimulation of human lymphocyte subpopulations by protein A from Staphylococcus aureus. Int Arch Allergy Appl Immunol. 1980;61(4):394–406. doi: 10.1159/000232467. [DOI] [PubMed] [Google Scholar]
  39. Trotter J., Steinman L. Homing of Lyt-2+ and Lyt-2- T cell subsets and B lymphocytes to the central nervous system of mice with acute experimental allergic encephalomyelitis. J Immunol. 1984 Jun;132(6):2919–2923. [PubMed] [Google Scholar]
  40. Van Epps D. E., Potter J. W., Durant D. A. Production of a human T lymphocyte chemotactic factor by T cell subpopulations. J Immunol. 1983 Jun;130(6):2727–2731. [PubMed] [Google Scholar]
  41. Vercellotti G. M., McCarthy J., Furcht L. T., Jacob H. S., Moldow C. F. Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion. Blood. 1983 Nov;62(5):1063–1069. [PubMed] [Google Scholar]
  42. Wall R. T., Cooper S. L., Kosek J. C. The influence of exogenous fibronectin on blood granulocyte adherence to vascular endothelium in vitro. Exp Cell Res. 1982 Jul;140(1):105–109. doi: 10.1016/0014-4827(82)90161-6. [DOI] [PubMed] [Google Scholar]
  43. Watson A. J., DeMars R., Trowbridge I. S., Bach F. H. Detection of a novel human class II HLA antigen. 1983 Jul 28-Aug 3Nature. 304(5924):358–361. doi: 10.1038/304358a0. [DOI] [PubMed] [Google Scholar]
  44. Woodruff J. J., Katz M., Lucas L. E., Stamper H. B., Jr An in vitro model of lymphocyte homing. II. Membrane and cytoplasmic events involved in lymphocyte adherence to specialized high-endothelial venules of lymph nodes. J Immunol. 1977 Nov;119(5):1603–1610. [PubMed] [Google Scholar]
  45. de Waal R. M., Bogman M. J., Maass C. N., Cornelissen L. M., Tax W. J., Koene R. A. Variable expression of Ia antigens on the vascular endothelium of mouse skin allografts. Nature. 1983 Jun 2;303(5916):426–429. doi: 10.1038/303426a0. [DOI] [PubMed] [Google Scholar]
  46. van Dinther-Janssen A. C., van Maarsseveen A. C., de Groot J., Scheper R. J. Comparative migration of T- and B-lymphocyte subpopulations into skin inflammatory sites. Immunology. 1983 Mar;48(3):519–527. [PMC free article] [PubMed] [Google Scholar]

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