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Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node

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    Rights statement: JEM © The Rockefeller University Press 2005

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http://jem.rupress.org/content/202/6/771
Original languageEnglish
Pages (from-to)771-81
Number of pages11
JournalJournal of Experimental Medicine
Volume202
Issue number6
DOIs
Publication statusPublished - 2005

Abstract

This study investigated the unresolved issue of antigen-dependency and antigen-specificity of autoimmune disease suppression by CD4+CD25+ T cells (T regs). Based on autoimmune ovarian disease (AOD) in day 3 thymectomized (d3tx) mice and polyclonal T regs expressing the Thy1.1 marker, we determined: (a) the location of recipient T cell suppression, (b) the distribution of AOD-suppressing T regs, and (c) the relative efficacy of male versus female T regs. Expansion of recipient CD4+ T cells, activation/memory marker expression, and IFN-gamma production were inhibited persistently in the ovary-draining LNs but not elsewhere. The cellular changes were reversed upon Thy1.1+ T reg depletion, with emergence of potent pathogenic T cells and severe AOD. Similar changes were detected in the regional LNs during autoimmune dacryoadenitis and autoimmune prostatitis suppression. Although the infused Thy1.1+ T regs proliferated and were disseminated in peripheral lymphoid organs, only those retrieved from ovary-draining LNs adoptively suppressed AOD at a suboptimal cell dose. By depriving d3tx recipients of ovarian antigens, we unmasked the supremacy of ovarian antigen-exposed female over male T regs in AOD suppression. Thus, disease suppression by polyclonal T regs depends on endogenous antigen stimulation; this occurs in a location where potent antigen-specific T regs accumulate and continuously negate pathogenic T cell response.

    Research areas

  • Animals, Autoimmune Diseases, Clone Cells, Epitopes, T-Lymphocyte, female, Lymph Nodes, Lymphocyte Activation, Male, MICE, mice, imbred A, Mice, Inbred C57BL, ovarian diseases, Receptors, Interleukin-2, Spleen , T-LYMPHOCYTE, REGULATORY

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