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. 1996 Oct;89(2):220–226. doi: 10.1046/j.1365-2567.1996.d01-736.x

Alloproliferation of purified CD4+ T cells to adult human heart endothelial cells, and study of second-signal requirements.

R M McDouall 1, C S Page 1, S Hafizi 1, M H Yacoub 1, M L Rose 1
PMCID: PMC1456493  PMID: 8943718

Abstract

Human endothelial cells have been shown to be capable of causing direct allostimulation of T cells. However, the majority of immunological studies of human endothelial cells have been performed on cells of fetal origin. Here we use endothelial cells isolated from the adult human heart, both large vessel (coronary artery, pulmonary artery and aorta) and also microvascular. We have examined the ability of all these endothelial cells to cause direct allostimulation of T cells, and show that purified CD4+ T cells can proliferate in response to adult human heart endothelial cells, the response being dependent on pretreatment of the endothelial cells with interferon-gamma (IFN-gamma) and inhibited by anti-HLA-DR monoclonal antibody. The proliferative responses of CD8+ T cells to adult but not fetal endothelial cells was inconsistent and weak. Proliferative responses were not blocked by CTLA4-Ig, which inhibits T-cell responses to "classical' antigen-presenting cells (APC), but > 50% inhibition was achieved with monoclonal antibody to lymphocyte function-associated antigen-3 (LFA-3). These results show that adult human cardiovascular endothelial cells are capable of causing allostimulation of resting CD4+ T cells, using a different second signal to classical APC. In view of these findings endothelial cells should be considered as APC following solid organ transplantation.

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Selected References

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  1. Auerbach R., Alby L., Morrissey L. W., Tu M., Joseph J. Expression of organ-specific antigens on capillary endothelial cells. Microvasc Res. 1985 May;29(3):401–411. doi: 10.1016/0026-2862(85)90028-7. [DOI] [PubMed] [Google Scholar]
  2. Boussiotis V. A., Freeman G. J., Gribben J. G., Daley J., Gray G., Nadler L. M. Activated human B lymphocytes express three CTLA-4 counterreceptors that costimulate T-cell activation. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11059–11063. doi: 10.1073/pnas.90.23.11059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Colson Y. L., Markus B. H., Zeevi A., Duquesnoy R. J. Adherence of alloreactive lymphocytes to human arterial endothelial cell monolayers. Clin Exp Immunol. 1989 Aug;77(2):206–210. [PMC free article] [PubMed] [Google Scholar]
  4. Colson Y. L., Markus B. H., Zeevi A., Duquesnoy R. J. Increased lymphocyte adherence to human arterial endothelial cell monolayers in the context of allorecognition. J Immunol. 1990 Apr 15;144(8):2975–2984. [PubMed] [Google Scholar]
  5. Edgell C. J., McDonald C. C., Graham J. B. Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3734–3737. doi: 10.1073/pnas.80.12.3734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Epperson D. E., Pober J. S. Antigen-presenting function of human endothelial cells. Direct activation of resting CD8 T cells. J Immunol. 1994 Dec 15;153(12):5402–5412. [PubMed] [Google Scholar]
  7. Freedman A. S., Freeman G., Horowitz J. C., Daley J., Nadler L. M. B7, a B-cell-restricted antigen that identifies preactivated B cells. J Immunol. 1987 Nov 15;139(10):3260–3267. [PubMed] [Google Scholar]
  8. Geppert T. D., Lipsky P. E. Antigen presentation at the inflammatory site. Crit Rev Immunol. 1989;9(4):313–362. [PubMed] [Google Scholar]
  9. Hirschberg H., Braathen L. R., Thorsby E. Antigen presentation by vascular endothelial cells and epidermal Langerhans cells: the role of HLA-DR. Immunol Rev. 1982;66:57–77. doi: 10.1111/j.1600-065x.1982.tb00434.x. [DOI] [PubMed] [Google Scholar]
  10. Hughes C. C., Savage C. O., Pober J. S. The endothelial cell as a regulator of T-cell function. Immunol Rev. 1990 Oct;117:85–102. doi: 10.1111/j.1600-065x.1990.tb00568.x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Janeway C. Immunogenicity signals 1,2,3 ... and 0. Immunol Today. 1989 Sep;10(9):283–286. doi: 10.1016/0167-5699(89)90081-9. [DOI] [PubMed] [Google Scholar]
  13. Kumar S., West D. C., Ager A. Heterogeneity in endothelial cells from large vessels and microvessels. Differentiation. 1987;36(1):57–70. doi: 10.1111/j.1432-0436.1987.tb00181.x. [DOI] [PubMed] [Google Scholar]
  14. Linsley P. S., Ledbetter J. A. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol. 1993;11:191–212. doi: 10.1146/annurev.iy.11.040193.001203. [DOI] [PubMed] [Google Scholar]
  15. Lodge P. A., Haisch C. E., Huber S. A., Martin B., Craighead J. C. Biological differences in endothelial cells depending upon organ derivation. Transplant Proc. 1991 Feb;23(1 Pt 1):216–218. [PubMed] [Google Scholar]
  16. McDouall R. M., Yacoub M., Rose M. L. Isolation, culture, and characterisation of MHC class II-positive microvascular endothelial cells from the human heart. Microvasc Res. 1996 Mar;51(2):137–152. doi: 10.1006/mvre.1996.0016. [DOI] [PubMed] [Google Scholar]
  17. Miossec P., Cavender D., Ziff M. Production of interleukin 1 by human endothelial cells. J Immunol. 1986 Apr 1;136(7):2486–2491. [PubMed] [Google Scholar]
  18. Murray A. G., Libby P., Pober J. S. Human vascular smooth muscle cells poorly co-stimulate and actively inhibit allogeneic CD4+ T cell proliferation in vitro. J Immunol. 1995 Jan 1;154(1):151–161. [PubMed] [Google Scholar]
  19. Page C. S., Holloway N., Smith H., Yacoub M., Rose M. L. Alloproliferative responses of purified CD4+ and CD8+ T cells to endothelial cells in the absence of contaminating accessory cells. Transplantation. 1994 Jun 15;57(11):1628–1637. [PubMed] [Google Scholar]
  20. Page C., Rose M., Yacoub M., Pigott R. Antigenic heterogeneity of vascular endothelium. Am J Pathol. 1992 Sep;141(3):673–683. [PMC free article] [PubMed] [Google Scholar]
  21. Page C., Thompson C., Yacoub M., Rose M. Human endothelial stimulation of allogeneic T cells via a CTLA-4 independent pathway. Transpl Immunol. 1994 Dec;2(4):342–347. doi: 10.1016/0966-3274(94)90013-2. [DOI] [PubMed] [Google Scholar]
  22. Petzelbauer P., Bender J. R., Wilson J., Pober J. S. Heterogeneity of dermal microvascular endothelial cell antigen expression and cytokine responsiveness in situ and in cell culture. J Immunol. 1993 Nov 1;151(9):5062–5072. [PubMed] [Google Scholar]
  23. 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]
  24. Rose M. L., Coles M. I., Griffin R. J., Pomerance A., Yacoub M. H. Expression of class I and class II major histocompatibility antigens in normal and transplanted human heart. Transplantation. 1986 Jun;41(6):776–780. doi: 10.1097/00007890-198606000-00021. [DOI] [PubMed] [Google Scholar]
  25. Savage C. O., Hughes C. C., McIntyre B. W., Picard J. K., Pober J. S. Human CD4+ T cells proliferate to HLA-DR+ allogeneic vascular endothelium. Identification of accessory interactions. Transplantation. 1993 Jul;56(1):128–134. doi: 10.1097/00007890-199307000-00024. [DOI] [PubMed] [Google Scholar]
  26. Savage C. O., Hughes C. C., Pepinsky R. B., Wallner B. P., Freedman A. S., Pober J. S. Endothelial cell lymphocyte function-associated antigen-3 and an unidentified ligand act in concert to provide costimulation to human peripheral blood CD4+ T cells. Cell Immunol. 1991 Oct 1;137(1):150–163. doi: 10.1016/0008-8749(91)90065-j. [DOI] [PubMed] [Google Scholar]
  27. Wagner C. R., Morris T. E., Shipley G. D., Hosenpud J. D. Regulation of human aortic endothelial cell-derived mesenchymal growth factors by allogeneic lymphocytes in vitro. A potential mechanism for cardiac allograft vasculopathy. J Clin Invest. 1993 Sep;92(3):1269–1277. doi: 10.1172/JCI116699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Westphal J. R., Willems H. W., Tax W. J., Koene R. A., Ruiter D. J., de Waal R. M. The proliferative response of human T cells to allogeneic IFN-gamma-treated endothelial cells is mediated via both CD2/LFA-3 and LFA-1/ICAM-1 and -2 adhesion pathways. Transpl Immunol. 1993;1(3):183–191. doi: 10.1016/0966-3274(93)90045-a. [DOI] [PubMed] [Google Scholar]
  29. Yokochi T., Holly R. D., Clark E. A. B lymphoblast antigen (BB-1) expressed on Epstein-Barr virus-activated B cell blasts, B lymphoblastoid cell lines, and Burkitt's lymphomas. J Immunol. 1982 Feb;128(2):823–827. [PubMed] [Google Scholar]
  30. Young J. W., Koulova L., Soergel S. A., Clark E. A., Steinman R. M., Dupont B. The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro. J Clin Invest. 1992 Jul;90(1):229–237. doi: 10.1172/JCI115840. [DOI] [PMC free article] [PubMed] [Google Scholar]

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