Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Sep 1;158(3):962–975. doi: 10.1084/jem.158.3.962

Allogeneic induction of the human T cell-instructed monocyte procoagulant response is rapid and is elicited by HLA-DR

PMCID: PMC2187098  PMID: 6224886

Abstract

The recognition of alloantigens by human lymphoid cells initiates a collaborative cellular pathway that rather rapidly induces in adherent cells (monocytes) the synthesis and expression of cell surface tissue factor, the initiating cofactor of the extrinsic coagulation pathway. This response was vigorous, generating tissue factor to a level nearly comparable to the response to endotoxin. However, it was temporally discordant with characterized lymphoid procoagulant responses to endotoxin, virus, and immune complexes in that it reached a maxima at 48 h, well after these other responses but clearly much faster than the well recognized proliferative responses to allogeneic stimulation. Using the Daudi lymphoblastoid B cell line, the allogeneic response could be fully elicited in a dose-dependent fashion within 18 h. The induction of monocyte tissue factor required collaboration with T lymphocytes, in accord with previously described T cell-instructed monocyte responses. HLA-DR was implicated as the allogeneic signal by the ability of two monoclonal antibodies to completely block, in a dose- dependent fashion, the induction of this pathway. Notably, the allogeneic procoagulant response was quantitatively discordant with respect to the allogeneic proliferative response, suggesting differences in specificity. This relatively rapid response may be applicable to typing of determinants in the major histocompatibility complex that are not equivalently identified by alternative analyses, and may be significant in tissue transplantation. The cellular pathway, linking allogeneic recognition with induction of a monocyte response that initiates the coagulation pathway, represents a further example of the linkage between these biologic systems, and is consistent with a pathogenetic role in allograft rejection by the promotion of vascular thrombosis and interstitial fibrin accumulation.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Accolla R. S., Moretta A., Cerottini J. C. Allogeneic mixed lymphocyte reactions in humans: pretreatment of either the stimulator or the responder cell population with monoclonal anti-Ia antibodies leads to an inhibition of cell proliferation. J Immunol. 1981 Dec;127(6):2438–2442. [PubMed] [Google Scholar]
  2. Albrechtsen D., Solheim B. G., Thorsey E. Antiserum inhibition of the mixed lymphocyte culture (MLC) interaction. Inhibitory effect of antibodies reactive with HLA-D-associated determinants. Cell Immunol. 1977 Feb;28(2):258–273. doi: 10.1016/0008-8749(77)90110-1. [DOI] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Amrani D., Mosesson M. W., Bianco C. Receptors for cold-insoluble globulin (plasma fibronectin) on human monocytes. J Exp Med. 1981 Jan 1;153(1):42–60. doi: 10.1084/jem.153.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DuPont B., Hansen J. A. Human mixed-lymphocyte culture reaction: genetics, specificity, and biological implications. Adv Immunol. 1976;23:107–202. doi: 10.1016/s0065-2776(08)60320-x. [DOI] [PubMed] [Google Scholar]
  5. Dvorak H. F., Mihm M. C., Jr, Dvorak A. M., Barnes B. A., Manseau E. J., Galli S. J. Rejection of first-set skin allografts in man. the microvasculature is the critical target of the immune response. J Exp Med. 1979 Aug 1;150(2):322–337. doi: 10.1084/jem.150.2.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Geczy C. L., Meyer P. A. Leukocyte procoagulant activity in man: an in vitro correlate of delayed-type hypersensitivity. J Immunol. 1982 Jan;128(1):331–336. [PubMed] [Google Scholar]
  7. Goyert S. M., Silver J. Isolation of I-A subregion-like molecules from subhuman primates and man. Nature. 1981 Nov 19;294(5838):266–268. doi: 10.1038/294266a0. [DOI] [PubMed] [Google Scholar]
  8. HENRY L., MARSHALL D. C., FRIEDMAN E. A., DAMMIN G. J., MERRILL J. P. The rejection of skin homografts in the normal human subject. II. Histological findings. J Clin Invest. 1962 Mar;41:420–446. doi: 10.1172/JCI104496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Halloran P., Aprile M., Haddad G., Robinette M. The significance of elevated procoagulant activity in the monocytes of renal transplant recipients. Transplant Proc. 1982 Dec;14(4):669–672. [PubMed] [Google Scholar]
  10. Hattler B. G., Jr, Rocklin R. E., Ward P. A., Rickles F. R. Functional features of lymphocytes recovered from a human renal allograft. Cell Immunol. 1973 Nov;9(2):289–296. doi: 10.1016/0008-8749(73)90080-4. [DOI] [PubMed] [Google Scholar]
  11. Huber C., Fink U., Leibold W., Schmalzl F., Peterson P. A., Klareskog L., Braunsteiner H. The role of adherent HLA-DR+ mononuclear cells in autologous and allogeneic MLR. J Immunol. 1981 Aug;127(2):726–731. [PubMed] [Google Scholar]
  12. Indiveri F., Wilson B. S., Russo C., Quaranta V., Pellegrino M. A., Ferrone S. Ia-like antigens on human T lymphocytes: relationship to other surface markers, role in mixed lymphocyte reactions, and structural profile. J Immunol. 1980 Dec;125(6):2673–2678. [PubMed] [Google Scholar]
  13. 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]
  14. Kung P. C., Goldstein G. Functional and developmental compartments of human T lymphocytes. Vox Sang. 1980 Sep;39(3):121–127. doi: 10.1111/j.1423-0410.1980.tb01846.x. [DOI] [PubMed] [Google Scholar]
  15. Ledbetter J. A., Evans R. L., Lipinski M., Cunningham-Rundles C., Good R. A., Herzenberg L. A. Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man. J Exp Med. 1981 Feb 1;153(2):310–323. doi: 10.1084/jem.153.2.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Levy G. A., Edgington T. S. Lymphocyte cooperation is required for amplification of macrophage procoagulant activity. J Exp Med. 1980 May 1;151(5):1232–1244. doi: 10.1084/jem.151.5.1232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Levy G. A., Edgington T. S. The major histocompatibility complex requirement for cellular collaboration in the murine lymphoid procoagulant response stimulated by bacterial lipopolysaccharide. J Immunol. 1982 Mar;128(3):1284–1288. [PubMed] [Google Scholar]
  18. Levy G. A., Leibowitz J. L., Edgington T. S. Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice. J Exp Med. 1981 Oct 1;154(4):1150–1163. doi: 10.1084/jem.154.4.1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Nemerson Y., Pitlick F. A. Purification and characterization of the protein component of tissue factor. Biochemistry. 1970 Dec 22;9(26):5100–5105. doi: 10.1021/bi00828a009. [DOI] [PubMed] [Google Scholar]
  21. Newman W., Gordon S., Hämmerling U., Senik A., Bloom B. R. Production of migration inhibition factor (MIF) and an inducer of plasminogen activator (IPA) by subsets of T cells in MLC. J Immunol. 1978 Mar;120(3):927–931. [PubMed] [Google Scholar]
  22. Niemetz J., Morrison D. C. Lipid A as the biologically active moiety in bacterial endotoxin (LPS)-initiated generation of procoagulant activity by peripheral blood leukocytes. Blood. 1977 Jun;49(6):947–956. [PubMed] [Google Scholar]
  23. Reinherz E. L., Kung P. C., Pesando J. M., Ritz J., Goldstein G., Schlossman S. F. Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression. J Exp Med. 1979 Dec 1;150(6):1472–1482. doi: 10.1084/jem.150.6.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rickles F. R., Levin J., Hardin J. A., Barr C. F., Conrad M. E., Jr Tissue factor generation by human mononuclear cells: effects of endotoxin and dissociation of tissue factor generation from mitogenic response. J Lab Clin Med. 1977 Apr;89(4):792–803. [PubMed] [Google Scholar]
  25. Rickles F. R., Rick P. D. Structural features of Salmonella typhimurium lipopolysaccharide required for activation of tissue factor in human mononuclear cells. J Clin Invest. 1977 Jun;59(6):1188–1195. doi: 10.1172/JCI108743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rothberger H., Zimmerman T. S., Spiegelberg H. L., Vaughan J. H. Leukocyte procoagulant activity: enhancement of production in vitro by IgG and antigen-antibody complexes. J Clin Invest. 1977 Mar;59(3):549–557. doi: 10.1172/JCI108670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rothberger H., Zimmerman T. S., Vaughan J. H. Increased production and expression of tissue thromboplastin-like procoagulant activity in vitro by allogeneically stimulated human leukocytes. J Clin Invest. 1978 Sep;62(3):649–655. doi: 10.1172/JCI109172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Russo C., Indiveri F., Quaranta V., Molinaro G. A., Pellegrino M. A., Ferrone S. Stimulation of human T lymphocytes by PHA-activated autologous T lymphocytes: analysis of the role of Ia-like antigens with monoclonal antibodies. Immunogenetics. 1981;12(3-4):267–274. doi: 10.1007/BF01561669. [DOI] [PubMed] [Google Scholar]
  29. Schwartz B. S., Edgington T. S. Immune complex-induced human monocyte procoagulant activity. I. a rapid unidirectional lymphocyte-instructed pathway. J Exp Med. 1981 Sep 1;154(3):892–906. doi: 10.1084/jem.154.3.892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schwartz B. S., Levy G. A., Curtiss L. K., Fair D. S., Edgington T. S. Plasma lipoprotein induction and suppression of the generation of cellular procoagulant activity in vitro: two procoagulant activities are produced by peripheral blood mononuclear cells. J Clin Invest. 1981 Jun;67(6):1650–1658. doi: 10.1172/JCI110201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schwartz B. S., Levy G. A., Fair D. S., Edgington T. S. Murine lymphoid procoagulant activity induced by bacterial lipopolysaccharide and immune complexes is a monocyte prothrombinase. J Exp Med. 1982 May 1;155(5):1464–1479. doi: 10.1084/jem.155.5.1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. van Ginkel C. J., Zeijlemaker W. P., Stricker L. A., Oh J. I., van Aken W. G. Enhancement of monocyte thromboplastin activity by antigenically stimulated lymphocytes: a link between immune reactivity and blood coagulation. Eur J Immunol. 1981 Jul;11(7):579–583. doi: 10.1002/eji.1830110711. [DOI] [PubMed] [Google Scholar]
  33. von Willebrand E., Häyry P. Composition and in vitro cytotoxicity of cellular infiltrates in rejecting human kidney allografts. Cell Immunol. 1978 Dec;41(2):358–372. doi: 10.1016/0008-8749(78)90233-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES