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. 1991 Feb;72(2):269–276.

Differences in the stimulating capacity of immobilized anti-CD3 monoclonal antibodies: variable dependence on interleukin-1 as a helper signal for T-cell activation.

J Verwilghen 1, M L Baroja 1, F Van Vaeck 1, J Van Damme 1, J L Ceuppens 1
PMCID: PMC1384495  PMID: 1826671

Abstract

Monoclonal antibodies to the CD3 antigen on human T lymphocytes have been shown to induce accessory cell-dependent T-cell activation. One function of the accessory cells is cross-linking of CD3 by Fc receptor-binding of the anti-CD3 antibodies. Whether additional accessory signals are still required when anti-CD3 is presented in immobilized form is controversial. In the present study we stimulated purified human T cells with several anti-CD3 monoclonal antibodies, which were immobilized by coating the culture wells with goat anti-mouse IgG. A first group of immobilized anti-CD3 antibodies (anti-Leu-4, UCHT1, anti-T3, WT32 and 64.1) induced vigorous T-cell proliferation in the complete absence of monocytes, even when anti-interleukin-1 beta antiserum was added to the cultures. Other immobilized anti-CD3 antibodies (OKT3, WT31) required interleukin-1 beta in order to induce T-cell proliferation. However, when OKT3 was immobilized by direct coating of the culture wells with OKT3, it was also able to induce accessory cell-independent production of interleukin-2 and T-cell proliferation. Interleukin-1 beta further enhanced the interleukin-2-dependent proliferative response and it could provide help to induce proliferation at doses of immobilized OKT3 which, by themselves, were insufficient for full T-cell activation. We conclude that the requirement for interleukin-1 beta to induce interleukin-2-dependent proliferation of T cells when stimulated with anti-CD3 antibodies is not absolute, but depends on the CD3 epitope recognized, on the way of antibody presentation, on the antibody concentration and on other, still undefined, characteristics of the monoclonal antibodies used.

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Selected References

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

  1. Baroja M. L., Ceuppens J. L. More exact quantification of interleukin-2 production by addition of anti-Tac monoclonal antibody to cultures of stimulated lymphocytes. J Immunol Methods. 1987 Apr 16;98(2):267–270. doi: 10.1016/0022-1759(87)90014-7. [DOI] [PubMed] [Google Scholar]
  2. Burns G. F., Boyd A. W., Beverley P. C. Two monoclonal anti-human T lymphocyte antibodies have similar biologic effects and recognize the same cell surface antigen. J Immunol. 1982 Oct;129(4):1451–1457. [PubMed] [Google Scholar]
  3. Ceuppens J. L., Baroja M. L., Lorre K., Van Damme J., Billiau A. Human T cell activation with phytohemagglutinin. The function of IL-6 as an accessory signal. J Immunol. 1988 Dec 1;141(11):3868–3874. [PubMed] [Google Scholar]
  4. Ceuppens J. L., Baroja M. L. Monoclonal antibodies to the CD5 antigen can provide the necessary second signal for activation of isolated resting T cells by solid-phase-bound OKT3. J Immunol. 1986 Sep 15;137(6):1816–1821. [PubMed] [Google Scholar]
  5. Ceuppens J. L., Bloemmen F. J., Van Wauwe J. P. T cell unresponsiveness to the mitogenic activity of OKT3 antibody results from a deficiency of monocyte Fc gamma receptors for murine IgG2a and inability to cross-link the T3-Ti complex. J Immunol. 1985 Dec;135(6):3882–3886. [PubMed] [Google Scholar]
  6. Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
  7. Geppert T. D., Lipsky P. E. Accessory cell independent proliferation of human T4 cells stimulated by immobilized monoclonal antibodies to CD3. J Immunol. 1987 Mar 15;138(6):1660–1666. [PubMed] [Google Scholar]
  8. Geppert T. D., Lipsky P. E. Activation of T lymphocytes by immobilized monoclonal antibodies to CD3. Regulatory influences of monoclonal antibodies to additional T cell surface determinants. J Clin Invest. 1988 May;81(5):1497–1505. doi: 10.1172/JCI113481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Halvorsen R., Gaudernack G., Leivestad T., Vartdal F., Thorsby E. Activation of resting, pure CD4+, and CD8+ cells via CD3. Requirements for second signals. Scand J Immunol. 1987 Aug;26(2):197–205. doi: 10.1111/j.1365-3083.1987.tb02252.x. [DOI] [PubMed] [Google Scholar]
  10. Kawakami K., Yamamoto Y., Kakimoto K., Onoue K. Requirement for delivery of signals by physical interaction and soluble factors from accessory cells in the induction of receptor-mediated T cell proliferation. Effectiveness of IFN-gamma modulation of accessory cells for physical interaction with T cells. J Immunol. 1989 Mar 15;142(6):1818–1825. [PubMed] [Google Scholar]
  11. Ledbetter J. A., June C. H., Martin P. J., Spooner C. E., Hansen J. A., Meier K. E. Valency of CD3 binding and internalization of the CD3 cell-surface complex control T cell responses to second signals: distinction between effects on protein kinase C, cytoplasmic free calcium, and proliferation. J Immunol. 1986 Jun 1;136(11):3945–3952. [PubMed] [Google Scholar]
  12. 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]
  13. Meuer S. C., Hussey R. E., Cantrell D. A., Hodgdon J. C., Schlossman S. F., Smith K. A., Reinherz E. L. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. doi: 10.1073/pnas.81.5.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Meuer S. C., Meyer zum Büschenfelde K. H. T cell receptor triggering induces responsiveness to interleukin 1 and interleukin 2 but does not lead to T cell proliferation. J Immunol. 1986 Jun 1;136(11):4106–4112. [PubMed] [Google Scholar]
  15. Palacios R. Mechanisms by which accessory cells contribute in growth of resting T lymphocytes initiated by OKT3 antibody. Eur J Immunol. 1985 Jul;15(7):645–651. doi: 10.1002/eji.1830150702. [DOI] [PubMed] [Google Scholar]
  16. Pichler W. J., Walker C., Bettens F., Koponen M., von Tscharner V., Kurrle R., Snow C., de Weck A. L. Differences of T-cell activation by the anti-CD3 antibodies Leu4 and BMA030. Cell Immunol. 1987 Aug;108(1):175–187. doi: 10.1016/0008-8749(87)90202-4. [DOI] [PubMed] [Google Scholar]
  17. Scheurich P., Ucer U., Wrann M., Pfizenmaier K. Early events during primary activation of T cells: antigen receptor cross-linking and interleukin 1 initiate proliferative response of human T cells. Eur J Immunol. 1985 Nov;15(11):1091–1095. doi: 10.1002/eji.1830151105. [DOI] [PubMed] [Google Scholar]
  18. Schwartz R. H. A cell culture model for T lymphocyte clonal anergy. Science. 1990 Jun 15;248(4961):1349–1356. doi: 10.1126/science.2113314. [DOI] [PubMed] [Google Scholar]
  19. Smith K. G., Austyn J. M., Hariri G., Beverley P. C., Morris P. J. T cell activation by anti-T3 antibodies: comparison of IgG1 and IgG2b switch variants and direct evidence for accessory function of macrophage Fc receptors. Eur J Immunol. 1986 May;16(5):478–486. doi: 10.1002/eji.1830160503. [DOI] [PubMed] [Google Scholar]
  20. Spits H., Borst J., Tax W., Capel P. J., Terhorst C., de Vries J. E. Characteristics of a monoclonal antibody (WT-31) that recognizes a common epitope on the human T cell receptor for antigen. J Immunol. 1985 Sep;135(3):1922–1928. [PubMed] [Google Scholar]
  21. Tax W. J., Hermes F. F., Willems R. W., Capel P. J., Koene R. A. Fc receptors for mouse IgG1 on human monocytes: polymorphism and role in antibody-induced T cell proliferation. J Immunol. 1984 Sep;133(3):1185–1189. [PubMed] [Google Scholar]
  22. Tunnacliffe A., Olsson C., de la Hera A. The majority of human CD3 epitopes are conferred by the epsilon chain. Int Immunol. 1989;1(5):546–550. doi: 10.1093/intimm/1.5.546. [DOI] [PubMed] [Google Scholar]
  23. Umetsu D. T., Katzen D., Chatila T., Miller R., Jabara H. H., Maher M., Oettgen H., Terhorst C., Geha R. S. Requirements for activation of human peripheral blood T cells by mouse monoclonal antibodies to CD3. Clin Immunol Immunopathol. 1987 Apr;43(1):48–64. doi: 10.1016/0090-1229(87)90156-5. [DOI] [PubMed] [Google Scholar]
  24. Van Damme J., De Ley M., Opdenakker G., Billiau A., De Somer P., Van Beeumen J. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature. 1985 Mar 21;314(6008):266–268. doi: 10.1038/314266a0. [DOI] [PubMed] [Google Scholar]
  25. Van Damme J., De Ley M., Van Snick J., Dinarello C. A., Billiau A. The role of interferon-beta 1 and the 26-kDa protein (interferon-beta 2) as mediators of the antiviral effect of interleukin 1 and tumor necrosis factor. J Immunol. 1987 Sep 15;139(6):1867–1872. [PubMed] [Google Scholar]
  26. Van Wauwe J. P., De Mey J. R., Goossens J. G. OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J Immunol. 1980 Jun;124(6):2708–2713. [PubMed] [Google Scholar]
  27. Vine J. B., Geppert T. D., Lipsky P. E. Precursor frequency of human T4 cells responding to stimulation through the CD3 molecular complex: role of various cytokines in promoting growth and IL2 production. Cell Immunol. 1989 Dec;124(2):212–226. doi: 10.1016/0008-8749(89)90126-3. [DOI] [PubMed] [Google Scholar]
  28. Walker C., Bettens F., Pichler W. J. Activation of T cells by cross-linking an anti-CD3 antibody with a second anti-T cell antibody: mechanism and subset-specific activation. Eur J Immunol. 1987 Jun;17(6):873–880. doi: 10.1002/eji.1830170622. [DOI] [PubMed] [Google Scholar]
  29. Williams J. M., Deloria D., Hansen J. A., Dinarello C. A., Loertscher R., Shapiro H. M., Strom T. B. The events of primary T cell activation can be staged by use of Sepharose-bound anti-T3 (64.1) monoclonal antibody and purified interleukin 1. J Immunol. 1985 Oct;135(4):2249–2255. [PubMed] [Google Scholar]

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