Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe<sup>-/-</sup> mice that artery TLOs (ATLOs) controlled highly territorialized aorta Tcell responses. ATLOs promoted Tcell recruitment, primed CD4<sup>+</sup> Tcells, generated CD4<sup>+</sup>, CD8<sup>+</sup>, T regulatory (Treg) effector and central memory cells, converted naive CD4<sup>+</sup> Tcells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle celllymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe<sup>-/-</sup>Ltbr<sup>-/-</sup> and to a similar extent in aged Apoe<sup>-/-</sup>Ltbr<sup>fl/fl</sup>Tagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta Tcell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs.
- vascular smooth muscle cells
- Lymphotoxin β receptors