Induction of oral immune tolerance in systemic lupus erythematosus-like murine model by recombinant nucleosomal universal Th cell epitope

To explore the feasibility of oral immune tolerance of systemic lupus erythematosus (SLE)-like model induced by nucleosomal Th cell epitope via the attenuated Salmonella typhimurium. SLE-like murine model was established by immunization with apoptotic syngeneic lymphocytes. The recombinant strains were orally administrated to induce immune tolerance. The levels of serum autoantibodies, such as anti-ANA, ds-DNA, and antinucleosome antibody, leukopenia, proteinuria and kidney injuries were evaluated. SLE-like murine model was successfully established. Compared with controls, it was shown that CTLA4-Ig-H2B group could dramatically reduce the levels of serum autoantibodies, such as anti-ANA, ds-DNA and antinucleosome antibody and ameliorate leukopenia and proteinuria (all P < 0.05). Immune complex deposits of IgG in glomeruli were lower in CTLA4-Ig-H2B (1.35 +/- 0.16) than in CTLA4-Ig (1.66 +/- 0.23) and H2B (1.69 +/- 0.24) (both P < 0.05). The score of glomeruli lesion of CTLA4-Ig-H2B (1.26 +/- 0.14) was significantly lower than those of CTLA4-Ig (1.73 +/- 0.25) and H2B (1.71 +/- 0.20) (both P < 0.05). Combined with CTLA4-Ig, it is feasible to induce oral immune tolerance of SLE models with nucleosomal Th cell epitope via the attenuated Salmonella typhimurium. This may provide a novel way to prevent and treat SLE by oral immune tolerance.