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 Cells1

• Published in: The Journal of immunology (1950) 2008-11, Vol.181 (9), p.6038-6050
• Main Authors: Wu, Henry Yim, Quintana, Francisco J., Weiner, Howard L.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606

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