Autoimmune CD4⁺T cells cause Meibomian gland dysfunction in an adoptive transfer model

Sjögren disease (SjD) is an autoimmune disease driven by autoimmune CD4⁺T cells that leads to an immune-mediated loss of lacrimal glands (LG). Meibomian glands are lipid-producing glands in the eyelids that help prevent tear evaporation. While the role of T cells in LG-mediated destruction is well established, it is unknown whether pathogenic T cells can cause MG dysfunction (MGD). Herein, we investigated whether autoimmune CD4⁺T cells induce MGD and characterized the pathophysiologic mechanisms using an adoptive transfer model. T cells were isolated from CD25KO (KO^CD4) or wild-type (WT^CD4) mice and transferred into Rag1KO mice. In comparison, KO cells were co-adoptively transferred with WT regulatory T cells (KO^CD4 + WT^Tregs). Our results demonstrate that CD25KO CD4⁺T recipients had MG dropout, CD4⁺IFN-γ⁺ infiltration, increased MHC II presentation within the periglandular area, MG fibrosis, decreased lipid production, and upregulation of pathways related to inflammation, including Type II interferon signaling. Rag1KO, WT^CD4, and KO^CD4 + WT^Tregs recipients exhibited minimal inflammation in the periglandular MG area. These results indicate that autoimmune CD4⁺T cells are sufficient to cause MGD, and healthy young regulatory T cells can prevent T-cell-mediated damage. Our findings provide mechanistic insights into the pathogenesis of autoimmune SjD and could impact how patients are managed in the clinic.