Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Jan;85(1):213–217. doi: 10.1073/pnas.85.1.213

Induction of expression of cell-surface homologous restriction factor upon anti-CD3 stimulation of human peripheral lymphocytes.

D E Martin 1, L S Zalman 1, H J Müller-Eberhard 1
PMCID: PMC279514  PMID: 2963326

Abstract

Homologous restriction factor (HRF) is a 65-kDa membrane protein that inhibits transmembrane channel formation by the membrane-attack complex of complement and by the complement component C9-related cytolytic lymphocyte protein. Stimulation of resting peripheral human lymphocytes with the anti-CD3 monoclonal antibody OKT3 has been shown to induce cytotoxicity in the CD8+ subpopulation. As demonstrated here, OKT3 stimulation also induces expression of cell-surface HRF by CD4+ and CD8+ T lymphocytes. The small proportion of Leu 19+ natural killer lymphocytes present in peripheral blood mononuclear cells was found to express HRF prior to stimulation. Whereas unstimulated peripheral blood mononuclear cells were susceptible to lysis by the membrane-attack complex or by the C9-related protein, OKT3-stimulated peripheral blood mononuclear cells were relatively resistant to both the membrane-attack complex and C9-related protein. This acquired resistance was abrogated by blocking surface HRF with F(ab')2 anti-HRF, suggesting that resistance was due to lymphocyte-membrane HRF. By using solid-phase anti-HRF, a 65-kDa protein was isolated from the activated peripheral blood mononuclear cells and shown to be capable of conferring upon sheep erythrocytes the characteristic activity of human HRF.

Full text

PDF
215

Images in this article

216Image
on p.216

Selected References

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

  1. Berke G. Interaction of cytotoxic T lymphocytes and target cells. Prog Allergy. 1980;27:69–133. [PubMed] [Google Scholar]
  2. Biesecker G., Müller-Eberhard H. J. The ninth component of human complement: purification and physicochemical characterization. J Immunol. 1980 Mar;124(3):1291–1296. [PubMed] [Google Scholar]
  3. Jung G., Honsik C. J., Reisfeld R. A., Müller-Eberhard H. J. Activation of human peripheral blood mononuclear cells by anti-T3: killing of tumor target cells coated with anti-target-anti-T3 conjugates. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4479–4483. doi: 10.1073/pnas.83.12.4479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Jung G., Martin D. E., Müller-Eberhard H. J. Induction of cytotoxicity in human peripheral blood mononuclear cells by monoclonal antibody OKT3. J Immunol. 1987 Jul 15;139(2):639–644. [PubMed] [Google Scholar]
  5. Klob W. P., Müller-Eberhard H. J. The membrane attack mechanism of complement: the three polypeptide chain structure of the eigth component (C8). J Exp Med. 1976 May 1;143(5):1131–1139. doi: 10.1084/jem.143.5.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kranz D. M., Eisen H. N. Resistance of cytotoxic T lymphocytes to lysis by a clone of cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1987 May;84(10):3375–3379. doi: 10.1073/pnas.84.10.3375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Manger B., Weiss A., Weyand C., Goronzy J., Stobo J. D. T cell activation: differences in the signals required for IL 2 production by nonactivated and activated T cells. J Immunol. 1985 Dec;135(6):3669–3673. [PubMed] [Google Scholar]
  8. Martin D. E., Zalman L. S., Jung G., Müller-Eberhard H. J. Induction of synthesis of the cytolytic C9 (ninth component of complement)-related protein in human peripheral mononuclear cells by monoclonal antibody OKT3 or interleukin 2: correlation with cytotoxicity and lymphocyte phenotype. Proc Natl Acad Sci U S A. 1987 May;84(9):2946–2950. doi: 10.1073/pnas.84.9.2946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Pangburn M. K., Schreiber R. D., Müller-Eberhard H. J. Deficiency of an erythrocyte membrane protein with complement regulatory activity in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5430–5434. doi: 10.1073/pnas.80.17.5430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Phillips J. H., Lanier L. L. Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med. 1986 Sep 1;164(3):814–825. doi: 10.1084/jem.164.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Podack E. R., Esser A. F., Biesecker G., Müller-Eberhard H. J. Membrane attack complex of complement: a structural analysis of its assembly. J Exp Med. 1980 Feb 1;151(2):301–313. doi: 10.1084/jem.151.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Podack E. R., Kolb W. P., Esser A. F., Müller-Eberhard H. J. Structural similarities between C6 and C7 of human complement. J Immunol. 1979 Sep;123(3):1071–1077. [PubMed] [Google Scholar]
  13. Schmidt R. E., MacDermott R. P., Bartley G., Bertovich M., Amato D. A., Austen K. F., Schlossman S. F., Stevens R. L., Ritz J. Specific release of proteoglycans from human natural killer cells during target lysis. Nature. 1985 Nov 21;318(6043):289–291. doi: 10.1038/318289a0. [DOI] [PubMed] [Google Scholar]
  14. Schwab R., Crow M. K., Russo C., Weksler M. E. Requirements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1. J Immunol. 1985 Sep;135(3):1714–1718. [PubMed] [Google Scholar]
  15. Schönermark S., Rauterberg E. W., Shin M. L., Löke S., Roelcke D., Hänsch G. M. Homologous species restriction in lysis of human erythrocytes: a membrane-derived protein with C8-binding capacity functions as an inhibitor. J Immunol. 1986 Mar 1;136(5):1772–1776. [PubMed] [Google Scholar]
  16. Tsoukas C. D., Landgraf B., Bentin J., Valentine M., Lotz M., Vaughan J. H., Carson D. A. Activation of resting T lymphocytes by anti-CD3 (T3) antibodies in the absence of monocytes. J Immunol. 1985 Sep;135(3):1719–1723. [PubMed] [Google Scholar]
  17. Zalman L. S., Brothers M. A., Chiu F. J., Müller-Eberhard H. J. Mechanism of cytotoxicity of human large granular lymphocytes: relationship of the cytotoxic lymphocyte protein to the ninth component (C9) of human complement. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5262–5266. doi: 10.1073/pnas.83.14.5262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zalman L. S., Brothers M. A., Müller-Eberhard H. J. A C9 related channel forming protein in the cytoplasmic granules of human large granular lymphocytes. Biosci Rep. 1985 Dec;5(12):1093–1100. doi: 10.1007/BF01119631. [DOI] [PubMed] [Google Scholar]
  19. Zalman L. S., Martin D. E., Jung G., Müller-Eberhard H. J. The cytolytic protein of human lymphocytes related to the ninth component (C9) of human complement: isolation from anti-CD3-activated peripheral blood mononuclear cells. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2426–2429. doi: 10.1073/pnas.84.8.2426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zalman L. S., Wood L. M., Müller-Eberhard H. J. Inhibition of antibody-dependent lymphocyte cytotoxicity by homologous restriction factor incorporated into target cell membranes. J Exp Med. 1987 Oct 1;166(4):947–955. doi: 10.1084/jem.166.4.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zalman L. S., Wood L. M., Müller-Eberhard H. J. Isolation of a human erythrocyte membrane protein capable of inhibiting expression of homologous complement transmembrane channels. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6975–6979. doi: 10.1073/pnas.83.18.6975. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES