In vivo tolerance breakdown with dendritic cells pulsed with U1A protein in non-autoimmune mice: the induction of a high level of autoantibodies but not renal pathological changes.

One of the hallmarks of systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), is the immune response to nuclear autoantigens. Several studies have proposed that dendritic cells may acquire the nuclear autoantigens from the apoptotic cells to initiate the systemic autoimmune responses. To examine the immune response to a nuclear autoantigen induced by dendritic cells, bone marrow-derived dendritic cells (BMDCs) pulsed with U1 small nuclear ribonucleoprotein (snRNP)-A protein (U1A) were intravenously injected into non-autoimmune mice. The results showed that BMDCs pulsed with U1A proteins by intravenous injection into BALB/c (H-2d) and DBA-2xNZW F1 (H-2d/u) mice were capable of activating the autoreactive T cells and inducing a high titre of immunoglobulin G (IgG) anti-U1A antibodies. Both groups of mice with a high anti-U1A autoantibody titre also transiently developed IgG against double-stranded (ds) DNA. However, unlike NZBxNZW F1 (BWF1) (H-2d/u) mice, no obviously histopathological changes to the glomeruli were noted in the mice treated either with BMDCs or with U1A-pulsed BMDCs. Several months after immunization, all mice treated with U1A-pulsed BMDCs did develop IgG, but not the complement C3 deposit in the glomeruli. The cytokine profile produced by the U1A-specific T cells of primed DBA-2xNZW F1 mice was skewed toward the T helper type 1 phenotype compared with that of BWF1 mice. The model we describe here adds to the further understanding of the pathogenic mechanisms, such as self-antigen shifting, and the mechanisms that account for the different responses to self-antigens when in a normal or an autoimmune state.