In the report by Heymann et al. in this issue of the JCI (10), a membrane-tethered form of OVA/hen egg lysozyme (mOVA/HEL) fusion antigen (Ag) expressed by glomerular podocytes, generated T cell– and DC–mediated GN in mice. (i) Antigen produced by podocytes is taken up by DCs in the kidney. (ii) Upon transfer of naive, OVA-specific CD8⁺ T cells to these transgenic mice, DCs within renal lymph nodes activate these T cells, causing clonal proliferation via antigen cross-presentation. (iii) Previously activated OVA-specific CD4⁺ T cells become further activated within the renal tissue by resident CD8^– DCs, which induces CCR5 ligand expression by CD4⁺ T cells and IL-12 secretion by DCs. The presence of CCR5 ligands draws activated CD8⁺ T cells from the renal lymph node to the kidney, and the IL-12 further promotes CTL effector activity. (iv) Lysis of OVA-bearing cells by CD8⁺ T cells releases more antigen, which is endocytosed by resident CD8^– DCs or drains to the renal lymph nodes, augmenting the response. (v) Additional macrophages, CD4⁺ T cells, CD8⁺ T cells, and DCs are recruited into the periglomerular space, further inducing glomerular injury. (vi) Depletion of diphtheria toxin–sensitive DCs after establishment of GN completely reverses immune infiltration pathology and restores normal glomerular microanatomy.