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Autoimmune Ovarian Disease in Day 3-Thymectomized Mice: The Neonatal Time Window, Antigen Specificity of Disease Suppression, and Genetic Control

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CD4+CD25+ Regulatory T Cells: Origin, Function and Therapeutic Potential

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 293))

Abstract

Discovery of the CD4+CD25+ T cells has stemmed from investigation of the AOD in the d3tx mice. Besides CD4+CD25+ T cell depletion, d3tx disease induction requires effector T cell activation prompted by lymphopenia. This is supported by other neonatal AOD models in which T cell-mediated injury has been found to be triggered by immune complex or Ag immunization. In addition, there is growing evidence that support a state of neonatal propensity to autoimmunity, which depends on concomitant endogenous antigenic stimulation, concomitant nematode infection, resistance to CD4+CD25+ T cell regulation, and participation of the neonatal innate system. The suppression of d3tx disease by polyclonal CD4+CD25+ T cells appears to be dependent on endogenous Ag and the persistence of regulatory T cells. Thus, suppression of AOD occurs in the ovarian LN, and AOD emerges upon ablation of the input regulatory T cells; and in AIP, the hormone-induced expression of prostate Ag in the CD4+CD25+ T cell donors rapidly enhances the capacity to suppress disease over Ag negative donors. Finally, genetic analysis of AOD and its component phenotypes has uncovered seven Aod loci. As the general themes that emerged, significant epistatic interactions among the loci play a role in controlling disease susceptibility, the majority of the Aod loci are linked to susceptibility loci of other autoimmune diseases, and the genetic intervals encompass candidate genes that are differentially expressed between CD4+CD25+ T cells and other T cells. The candidate genes include Pdcd1, TNFR superfamily genes, H2, Il2, Tgfb, Nalp5 or Mater, an oocyte auto Ag that reacts with autoantibody in sera of d3tx mice.

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Authors and Affiliations

  1. Department of Pathology, Health Science Center, University of Virginia, P.O. Box 800214, Charlottesville, VA, 22908, USA

    K. S. K. Tun & Y. Y. Setiady

  2. Department of Microbiology, University of Virginia, Charlottesville, VA, 22908, USA

    E. T. Samy

  3. Department of Medicine, University of Virginia, Charlottesville, VA, 22908, USA

    J. Lewis

  4. Departments of Medicine and Pathology, University of Vermont, Burlington, VT, 05405, USA

    C. Teuscher

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Editors and Affiliations

  1. Atlanta, Georgia

    R.W. Compans

  2. Birmingham, Alabama

    M.D. Cooper

  3. Kyoto

    T. Honjo

  4. Philadelphia, Pennsylvania

    H. Koprowski

  5. Basel

    F. Melchers

  6. La Jolla, California

    M.B.A. Oldstone  & P.K. Vogt  & 

  7. Oslo

    S. Olsnes

  8. Bethesda, Maryland

    M. Potter

  9. Munich

    H. Wagner

  10. Abteilung Entwicklungsimmunologie, Deutsches Krebsforschungszentrum Forschungsschwerpunkt Tumorimmunologie, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Bruno Kyewski

  11. Abteilung Immungenetik, Deutsches Krebsforschungszentrum Forschungsschwerpunkt Tumorimmunologie, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Elisabeth Suri-Payer

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Tun, K.S.K., Setiady, Y.Y., Samy, E.T., Lewis, J., Teuscher, C. (2005). Autoimmune Ovarian Disease in Day 3-Thymectomized Mice: The Neonatal Time Window, Antigen Specificity of Disease Suppression, and Genetic Control. In: Compans, R., et al. CD4+CD25+ Regulatory T Cells: Origin, Function and Therapeutic Potential. Current Topics in Microbiology and Immunology, vol 293. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27702-1_10

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