Role of Dendritic Cells in Induction of Tolerance and Immunity in Vivo

  • Barbara Fazekas de St. Groth
  • Matthew C. Cook
  • Adrian L. Smith
  • Matthew E. Wikstrom
  • Antony Basten
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)


Despite the recent revolution in understanding the molecular mechanisms of T cell activation, the means by which naive CD4+ T cells become tolerant or immune in response to antigen remains controversial. Evidence from a number of experimental systems has suggested that the process of determining the phenotype (but not the specificity) of immune responses is initiated by APCs1,2. However not only is the precise signalling pathway between APCs and naive T cells still undefined, but the role of each particular type of APC in the initiation of diverse immune responses in vivo is unclear.


Dendritic Cell Adoptive Transfer Cell Tolerance Double Transgenic Mouse Immunodeficient Host 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Janeway, C. A. J. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol. Today 13: 11–16 (1992).Google Scholar
  2. 2.
    Fazekas de St. Groth, B. Regulation of the immune response–lessons from transgenic models. Aust. N.Z. J. Med. 25: 761–767 (1995).CrossRefGoogle Scholar
  3. 3.
    Seder, R. A., Paul, W. E., Davis, M. M., and Fazekas de St. Groth, B. The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4’ T cells from T cell receptor trans-genic mice. J. Exp. Med. 176: 1091–1098 (1992).PubMedCrossRefGoogle Scholar
  4. 4.
    Hsieh, C.-S., Heimberger, A. B., Gold, J. S., O’Garra, A., and Murphy, K. M. Differential regulation of T helper phenotype development by interleukins 4 and I0 in an aß T-cell-receptor transgenic system. P N. A. S. (U. S. A.) 89: 6065–6069 (1992).CrossRefGoogle Scholar
  5. 5.
    Duncan, D. D., and Swain, S. L. Role of antigen-presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages. Eur. J. Immunol. 24: 2506–2514 (1994).PubMedCrossRefGoogle Scholar
  6. 6.
    Cassell, D. J., and Schwartz, R. H. A quantitative analysis of antigen-presenting cell function: activated B cells stimulate naive CD4 T cells but are inferior to dendritic cells in providing costimulation. J. Exp. Med. 180: 1829–1840 (1994).PubMedCrossRefGoogle Scholar
  7. 7.
    Constant, S., Sant’Angelo, D., Pasqualini, T., Taylor, T., Levin, D., Flavell, R., and Bottomly, K. Peptide and protein antigens require distinct antigen-presenting cell subsets for the priming of CD4’ T cells. J. Immunol. 154: 4915–4923 (1995).PubMedGoogle Scholar
  8. 8.
    Sunshine, G. H., Jimmo, B. L., lanelli, C., and Jarvis, L. Strong priming of T cells adoptively transferred into scid mice. J. Exp. Med. 174: 1643–1656 (1991).CrossRefGoogle Scholar
  9. 9.
    Goroff, D. K., Holmes, J. M., Basin, H., Nisol, F., and Finkelman, F. D. Polyclonal activation of the murine immune system by an antibody to IgD: XI contribution of membrane IgD cross-linking to the generation of an in vivo polyclonal antibody response. J. Immunol. 146: 18–25 (1991).PubMedGoogle Scholar
  10. 10.
    Eynon, E. E., and Parker, D. C. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J. Exp. Med. 175: 131–138 (1992).PubMedCrossRefGoogle Scholar
  11. 11.
    Fuchs, E. J., and Matzinger, P. B cells turn off virgin but not memory T cells. Science 258: 1156–1159 (1992).PubMedCrossRefGoogle Scholar
  12. 12.
    Day, M. J., Tse, A. G. D., Puklavec, M., Simmonds, S. J., and Mason, D. W. Targeting autoantigen to B cells prevents the induction of a cell-mediated autoimmune disease in rats. J. Exp. Med. 175: 655–659 (1992).PubMedCrossRefGoogle Scholar
  13. 13.
    Ronchese, F., and Hausmann, B. B lymphocytes in vivo fail to prime naive T cells but can stimulate antigen-experienced T lymphocytes. J. Exp. Med. 177: 679–690 (1993).PubMedCrossRefGoogle Scholar
  14. 14.
    Webb, S., Morris, C., and Sprent, J. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 63: 1249–1256 (1990).PubMedCrossRefGoogle Scholar
  15. 15.
    Fulcher, D. A., Lyons, A. B., Korn, S. L., Cook, M. C., Koleda, C., Parish, C., Fazekas de St. Groth, B., and Basten, A. The fate of self-reactive B-cells depends primarily on the degree of antigen receptor engagement and availability of T-cell help. J. Exp. Med. 183: 2313–2328 (1996).PubMedCrossRefGoogle Scholar
  16. 16.
    Inaba, K., Metlay, J. R, Crowley, M. T., and Steinman, R. M. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J. Exp. Med. 172: 631–640 (1990).PubMedCrossRefGoogle Scholar
  17. 17.
    Fazekas de St. Groth, B., Patten, R. A., Ho, W. Y., Rock, E. P., and Davis, M. M. An analysis of T cell receptor-ligand interaction using a transgenic antigen model for T cell tolerance and T cell receptor mutagenesis. Academic Press. San Diego. (1992).Google Scholar
  18. 18.
    Goodnow, C. C., Crosbie, J., Adelstein, S., Lavoie, T. B., Smith-Gill, S. J., Brink, R. A., Pritchard-Briscoe, H., Wotherspoon, J. S., Loblay, R. H., Raphael, K., Trent, R. J., and Basten, A. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 334:676–682 (I 988).Google Scholar
  19. 19.
    Fazekas de St. Groth, B., Cook, M. C., and Smith, A. L. The role of T cells in the regulation of B cell tolerance. Int. Rev. Immunol. in press (1996).Google Scholar
  20. 20.
    Widera, G., Burkly, L. C., Pinkert, C. A., ‘Ringer, E. C., Cowing, C., Palmiter, R. D., Brinster, R. L., and Flavell, R. A. Transgenic mice selectively lacking MHC Class II (1-E) antigen expression on B cells: an in vivo approach to investigate la gene function. Cell 51: 175–187 (1987).Google Scholar
  21. 21.
    Marrack, P., Lo, D., Brinster, R., Palmiter, R., Burkly, L., Flavell, R. H., and Kappler, J. The effect of thymus environment on T cell development and tolerance. Cell 53: 627–634 (1988).PubMedCrossRefGoogle Scholar
  22. 22.
    HayGlass, K. T., Naides, S. J., Scott, C. F. J., Benacerraf, B., and Sy, M.-S. T cell development in B cell-deficient mice. IV. The role of the B cells as antigen-presenting cells in vivo. J. Immunol.:823–829 (1986).Google Scholar
  23. 23.
    Ron, Y., and Sprent, J. T cell priming in vivo: a major role for B cells in presenting antigen to T cells in lymph nodes. J. Immunol. 138: 2848–2856 (1987).PubMedGoogle Scholar
  24. 24.
    Janeway, C. A., Ron, J., and Katz, M. E. The B cell is the initiating antigen-presenting cell in peripheral lymph nodes. J. Immunol. 138: 1051–1055 (1987).PubMedGoogle Scholar
  25. 25.
    Liu, Y., Wu, Y., Ramarathinam, L., Guo, Y., Huszar, D., Trounstine, M., and Zhao, M. Gene-targeted B-deficient mice reveal a critical role for B cells in the CD4 T cell response. lat. Immunol. 7: 1353–1362 (1995).Google Scholar
  26. 26.
    Constant, S., Schweitzer, N., West, J., Ranney, P., and Bottomly, K. B lymphocytes can be competent antigen-presenting cells for priming CDC T cells to protein antigens in vivo. J. lnnnunol. 155: 3734–3741 (1995).Google Scholar
  27. 27.
    Epstein, M. M., Di Rosa. F., Jankovic, D., Slier, A., and Matzinger, P. Successful T cell priming in B cell-deficient mice. J. Exp. Med. 182: 915–922 (1995).PubMedCrossRefGoogle Scholar
  28. 28.
    Kurt-Jones, E. A., Llano, D., HayGlass, K. A., Benacerraf, B., Sy, M.-S., and Abbas. A. K. The role of antigen-presenting B cells in T cell priming in vivo. Studies of B cell-deficient mice. J. Immunol. 140: 3773 3778 (1988).Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Barbara Fazekas de St. Groth
    • 1
  • Matthew C. Cook
    • 1
  • Adrian L. Smith
    • 1
  • Matthew E. Wikstrom
    • 1
  • Antony Basten
    • 1
  1. 1.Medicine and Cell BiologyCentenary institute of CancerNewtown, SydneyAustralia

Personalised recommendations