Nasal Anti-CD3 Antibody Ameliorates Lupus by Inducing an IL-10-Secreting CD4 + CD25 − LAP + Regulatory T Cell and Is Associated with Down-Regulation of IL-17 + CD4 + ICOS + CXCR5 + Follicular Helper T Cells

摘要: Lupus is an Ab-mediated autoimmune disease. One of the potential contributors to development systemic lupus erythematosus a defect in naturally occurring CD4+CD25+ regulatory T cells. Thus, generation inducible cells that can control autoantibody responses avenue for treatment erythematosus. We have found nasal administration anti-CD3 mAb attenuated as well arrested ongoing two strains lupus-prone mice. Nasal induced CD4+CD25−latency-associated peptide (LAP)+ cell secreted high levels IL-10 and suppressed disease vivo via IL-10- TFG-β-dependent mechanisms. Disease suppression also occurred following adoptive transfer CD4+CD25−LAP+ from anti-CD3-treated animals Animals treated with had less glomerulonephritis diminished autoantibodies measured by both ELISA autoantigen microarrays. affected function CD4+ICOS+CXCR5+ follicular helper are required production. express IL-17 IL-21 these cytokines were down-regulated anti-CD3. Our results demonstrate induces suppress mice it associated down-regulation help