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. © 2011 Society for Mucosal Immunology.