Function of tertiary lymphoid structures in autoimmune disease – animal study model

Abstract

Systemic lupus erythematosus (SLE) and lupus nephritis (LN) is an autoimmune disease characterized by autoantibody production, immune complex formation, inflammation, and infiltrating immune cells. In this thesis the role of T cells in the initiation of tertiary lymphoid structure formation during the development of SLE and LN was investigated in a spontaneous lupus mouse model and in an imiquimod (IMQ) induced model. By using gene expression analyses (qPCR) and immunohistochemistry (IHC) and multicolored IHC (OPAL) we demonstrated an upregulation of both proinflammatory (Il-6) and anti-inflammatory (Il-10) cytokines in both models. Other genes of interest (Tnfsf11 and Ctla4) were shown to be upregulated in the antibody positive group and in relation to activation of T cells and other immune cells. Infiltrating CD3 cells were shown to increase during the development of SLE and LN and most of them were in aggregates resembling TLS or located within large functional TLS. Using Opal IHC, we showed an increased infiltration of PSGL-1 positive CD4 T cells in the TLS. These cells could be detected early within the pelvic wall of young mice. In conclusion, the early detection of specialized T cells within the kidney of lupus prone mice indicates an important role of these cells in the initiation and propagation of TLS.