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Urothelial antigen-specific CD4+ T cells function as direct effector cells and induce bladder autoimmune inflammation independent of CD8+ T cells.

Abstract
The role of CD4(+) T cells in bladder autoimmune inflammation has not been identified because of the lack of a proper animal model. We investigated CD4(+) T-cell responses to bladder urothelial ovalbumin (OVA), a model self-antigen (Ag), in transgenic URO-OVA mice. The expression of bladder urothelial OVA rendered mice unresponsive to OVA and resulted in quick clearance of Ag-specific CD4(+) T cells. Adoptive transfer of naive OVA-specific CD4(+) T cells led to exogenous T-cell proliferation, activation, and bladder infiltration but no inflammatory induction. In contrast, adoptive transfer of preactivated OVA-specific CD4(+) T cells induced bladder inflammation. Studies further demonstrated that CD4(+) T cells induced bladder inflammation in URO-OVA mice depleted of CD8(+) T cells or deficient in the recombinase activating gene-1 (Rag-1(-/-)). These results indicate that urothelial Ag-specific CD4(+) T cells can function as direct effector cells to induce bladder autoimmune inflammation independent of CD8(+) T cells.
AuthorsW Liu, X Chen, D P Evanoff, Y Luo
JournalMucosal immunology (Mucosal Immunol) Vol. 4 Issue 4 Pg. 428-37 (Jul 2011) ISSN: 1935-3456 [Electronic] United States
PMID21270773 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Ovalbumin
Topics
  • Adoptive Transfer
  • Animals
  • Autoimmune Diseases (immunology, pathology)
  • Autoimmunity (immunology)
  • CD4-Positive T-Lymphocytes (immunology)
  • CD8-Positive T-Lymphocytes (immunology)
  • Cystitis (immunology, pathology)
  • Immune Tolerance (immunology)
  • Lymphocyte Activation (immunology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin (immunology)
  • Urothelium (immunology, pathology)

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