FIGURE 2.

Formation of juxta-islet tertiary lymphoid structures during the progression of diabetes in NOD mice. (A) No lymphatics were detected in association with normal islets. (B) Podoplanin-expressing cells were present on the outside and inside the tertiary lymphoid structure that constituted the insulitis lesion. (C) Tertiary lymphoid structure were filled with CD4⁺ T cells that drained into neolymphatics associated with normal venules. (D) Three-dimensional rendering of a typical tertiary lymphoid structure surrounding an islet. The outsides were limited by LYVE-1⁺ cells, forming a sac that drained into a lymphatic associated with a CD31⁺ blood vessel. (E and F) CD8 T cells were rare within early IATLs as shown at 9 wk of age NOD mice by immunodetection (E) and flow cytometry of cells recovered from dissociated islets (F). Spleen was used as a control (percentages out of the CD3 gate are presented). Scale bars, 50 µm.