Autoimmune CD4 ⁺ T cells Cause Meibomian Gland Dysfunction

Sjögren disease (SjD) is an autoimmune disease driven by autoreactive CD4 ⁺ T cells that leads to an immune-mediated loss of lacrimal glands. Meibomian glands are lipid-producing glands in the eyelids that help prevent tear evaporation. While the role of T cells in lacrimal gland-mediated destruction is well established, it is unknown whether pathogenic T cells can cause MG dysfunction (MGD). Herein, we investigated whether autoreactive CD4 ⁺ T cells induce MGD and characterized the pathophysiologic mechanisms using an adoptive transfer model. T cells were isolated from CD25KO (CD4 ^KO ) or wild-type (CD4 ^WT ) mice, transferred into Rag1 KO mice. Further, CD4 ^KO cells were co-adoptively transferred with WT regulatory T cells (CD4 ^KO +Tregs ^WT ). Our results demonstrate that CD4 ^KO recipients had MG dropout, CD4 ⁺ IFN-γ ⁺ infiltration, increased MHC II presentation within the periglandular area, MG fibrosis, and decreased lipid production and upregulation of pathways related to inflammation, including Type II interferon signaling. Rag1 KO, CD4 ^WT , and CD4 ^KO +Tregs ^WT 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. Taken together, our findings provide mechanistic insights into the pathogenesis autoimmune SjD, and could impact how patients are managed in the clinic.