T Cell Activation by CD3 Antibodies

  • Roland Kurrle
  • Waltraud Seyfert
  • Armin Trautwein
  • Friedrich Robert Seiler

Abstract

Monoclonal antibodies which recognize the T3 antigen on human T cells have turned out to be excellent tools for analyzing T cell activation. The T3 antigen complex seems to be involved in specific immune functions, either as a receptor or as molecules functionally or physically associated with the receptor (1–3). In contrast to T cell activation by mitogens, the activation via anti-T3 antibodies seems to reflect antigen-specific lymphocyte stimulation. It is well established that mere binding of different anti-T3 antibodies triggers mitogenesis (4,5), induces the production of immune mediators like interferon (γ-IFN) and interleukin-2 (IL-2) (6–8), and blocks cytotoxic effector functions and antigen-specific proliferative responses (9). However, to date all studies of the activation of human T cells via the T3 antigen complex have been carried out with monoclonal antibodies of the IgG2a isotype (OKT3) or the IgG1 isotype (Leu-4, UCHT1). From the functional point of view the isotypes of anti-T3 antibodies seem to play a critical role in the efficiency and the mechanism of T cell activation. Whereas anti-T3 antibodies of the IgG2a isotype are highly effective in activating T cells from all donors by an IL2-dependent mechanism (8,10), for anti-T3 antibodies of IgG1 isotype nonresponsiveness caused by polymorphism in the accessory cell function has been described (11). Based on blocking experiments with Fc fragments of normal IgG (12,13) and analysis of different ethnic groups, the cause of nonresponsiveness seems to be genetic variations of the Fc-γ receptor of accessory cells (11,14).

Keywords

Leukemia Interferon Thymidine Azide Dium 

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References

  1. 1.
    Chang, T.W., P.C. Kung, S.P. Gingras, and G. Goldstein. 1981. Does OKT3 monoclonal antibody react with an antigen-recognition structure on human T cells? Proc. Natl. Acad. Sci. U.S.A. 78: 1805.PubMedCrossRefGoogle Scholar
  2. 2.
    Reinherz, E.L., S. Meuer, K.A. Fitzgerald, R.E. Hussey, H. Levine, and S.F. Schlossman. 1982. Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex. Cell 30: 735.PubMedCrossRefGoogle Scholar
  3. 3.
    Meuer, S.C., K.A. Fitzgerald, R.E. Hussey, J.C. Hodgdon, S.F. Schlossman, and E.L. Reinherz. 1983. Clonotypic structures involved in antigen-specific human T cell function. J. Exp. Med. 157: 705.PubMedCrossRefGoogle Scholar
  4. 4.
    Van Wauwe, J.P., J.R. De Mey, and J.G. Goossens. 1980. OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J. Immunol. 124: 2708.PubMedGoogle Scholar
  5. 5.
    Musiani, P., N. Maggiano, F.B. Aiello, L. Lauriola, F.O. Ranelletti, and M. Piantelli. 1984. Ia-and IgG-Fc receptor-positive accessory cell sustains peripheral T lymphocyte but not thymocyte mitogenesis induced by OKT3 monoclonal antibody. Cell. Immunol. 84: 333.PubMedCrossRefGoogle Scholar
  6. 6.
    Pang, R.H.L., Y.K. Yip, and J. Vilcek. 1981. Immune interferon induction by a monoclonal antibody specific for human T cells. Cell. Immunol. 64: 304.PubMedCrossRefGoogle Scholar
  7. 7.
    Welte, K., E. Platzer, C.Y. Wang, E.A. Rinnooy Kan, M.A.S. Moore, and R. Mertelsmann. 1983. OKT8 antibody inhibits OKT3-induced IL2 production and proliferation in OKT8+ cells. J. Immunol. 131: 2356.PubMedGoogle Scholar
  8. 8.
    Van Wauwe, J.P., J.G. Goossens, and P.C.L. Beverley. 1984. Human T lymphocyte activation by monoclonal antibodies; OKT3, but not UCHT1, triggers mitogenesis via an interleukin 2-dependent mechanism. J. Immunol. 133: 129.PubMedGoogle Scholar
  9. 9.
    Van Wauwe, J.P., J.G. Goossens, and G. Van Nyen. 1984. Inhibition of lymphocyte proliferation by monoclonal antibody directed against the T3 antigen on human T cells. Cell. Immunol. 86: 525.PubMedCrossRefGoogle Scholar
  10. 10.
    Meuer, S.C., R.E. Hussey, D.A. Cantrell, J.C. Hodgdon, S.F. Schlossmann, K.A. Smith, and E.L. Reinherz. 1984. 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. 81: 1509.PubMedCrossRefGoogle Scholar
  11. 11.
    Tax, W.J.M., H.W. Willems, P.P.M. Reekers, P.J.A. Capel, and R.A.P. Koene. 1983. Polymorphism in mitogenic effect of IgGI monoclonal antibodies against T3 antigen on human T cells. Nature 304: 445.PubMedCrossRefGoogle Scholar
  12. 12.
    Looney, R.J., and G.N. Abraham. 1984. The Fc portion of intact IgG blocks stimulation of human PBMC by anti-T3. J. Immunol. 133: 154.PubMedGoogle Scholar
  13. 13.
    Landegren, U., J. Andersson, and H. Wigzell. 1984. Mechanism of T lymphocyte activation by OKT-3 antibodies. A general model for T cell induction. Eur. J. Immunol. 14: 325.PubMedCrossRefGoogle Scholar
  14. 14.
    Abo, T., A.B. Tilden, C.M. Balch, K. Kumagai, G.M. Troup, and M.D. Cooper. 1984. Ethnic differences in the lymphocyte proliferative response induced by a murine IgGI antibody, Leu4, to the T3 molecule. J. Exp. Med. 160: 303.CrossRefGoogle Scholar
  15. 15.
    Russell, P.S., R.B. Colvin, and A.B. Cosini. 1984. Monoclonal antibodies for the diagnosis and treatment of transplant rejection. Ann. Rev. Med. 35: 63.PubMedCrossRefGoogle Scholar
  16. 16.
    Cosimi, A.B., R.C. Burton, R.B. Colvin, G. Goldstein, F.L. Delmonico, M.P. La Quaglia, N. Tolkoff-Rubin, R.H. Rubin, J.T. Herrin, and P.S. Russell. 1981. Treatment of acute renal allograft rejection with OKT3 monoclonal antibody. Transplantation 32: 535.PubMedCrossRefGoogle Scholar
  17. 17.
    Prentice, H.G., G. Janossy, D. Skeggs, H.A. Blacklock, K.F. Bradstock, G. Goldstein, and A.V. Hoffbrand. 1982. Use of anti-T-cell monoclonal antibody OKT3 to prevent acute Graft-Versus-Host disease in allogeneic bone-marrow transplantation for acute leukemia. Lancet 27: 700.CrossRefGoogle Scholar
  18. 18.
    Blacklock, H.A., H.G. Prentice, M.J.M.L. Gilmore, E. Price-Jones, S. Schey, N. Tidman, D.D.F. Ma, G. Goldstein, G. Janossy, and A.V. Hoffbrand. 1983. Attempts at T cell depletion using OKT3 and rabbit complement to prevent acute Graft-Versus-Host disease in allogeneic bone marrow transplantation. Exp. Hematol. 11: 37.Google Scholar
  19. 19.
    Estabrook, A., C.L. Berger, R. Mittler, P. LoGerfo, M. Hardy, and R.L. Edelson. 1983. Antigenic modulation of human T lymphocytes by monoclonal antibodies. Transplant. Proc. XV: 651.Google Scholar
  20. 20.
    Chatenoud, L., M.F. Baudrihaye, H. Kreis, G. Goldstein, J. Schindler, and J.F. Bach. 1982. Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody. Eur. J. Immunol. 12: 979.PubMedCrossRefGoogle Scholar
  21. 21.
    Kurrle, R., W. Seyfert, A. Trautwein, and F.R. Seiler. 1985. Cellular mechanisms of T-cell activation by modulation of the T3-antigen complex. Transplant. Proc. XVII: 880.Google Scholar
  22. 22.
    Hoffman, R.A., P.C. Kung, W.P. Hansen, and G. Goldstein. 1980. Simple and rapid measurement of human T lymphocytes and their subclasses in peripheral blood. Proc. Natl. Acad. Sci. U.S.A. 77: 4914.PubMedCrossRefGoogle Scholar
  23. 23.
    Leibson, H.J., M. Gefter, A. Zlotnik, P. Marrak, and J.W. Kappler. 1984. Role of y-interferon in antibody-producing responses. Nature 309: 799.PubMedCrossRefGoogle Scholar
  24. 24.
    Sidman, C.L., J.D. Marshall, L.D. Shultz, P.W. Gray, and H.M. Johnson. 1984. y-Interferon is one of several direct B cell-maturing lymphokines. Nature 309: 801.Google Scholar
  25. 25.
    Tax, W.J.M., H. Spits, H.F.M. Hermes, H.W. Willems, P.J. Capel, and R.A.P. Koene. 1984. Polymorphism of human Fc. J. Immunol. (in press).Google Scholar
  26. 26.
    Wong, G.H.W., J. Clark-Lewis, J.L. Mckimm-Breschkin, A.W. Harris, and J.W. Schrader. 1983. Interferon-y induces enhanced expression of Ia and H-2 antigens on B-lymphoid, macrophage, and myeloid cell lines. J. Immunol. 131: 788.PubMedGoogle Scholar
  27. 27.
    King, D.P. and P.P. Jones. 1983. Induction of Ia and H-2 antigens on a macrophage cell line by immune interferon. J. Immunol. 131: 315.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1986

Authors and Affiliations

  • Roland Kurrle
  • Waltraud Seyfert
  • Armin Trautwein
  • Friedrich Robert Seiler

There are no affiliations available

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