Loading...
Please wait, while we are loading the content...
Similar Documents
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
| Content Provider | Scilit |
|---|---|
| Author | Wu, Henry Yim Quintana, Francisco J. Weiner, Howard L. |
| Copyright Year | 2008 |
| Description | 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. |
| Ending Page | 6050 |
| Page Count | 13 |
| Starting Page | 6038 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.181.9.6038 |
| Journal | The Journal of Immunology |
| Issue Number | 9 |
| Volume Number | 181 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2008-11-01 |
| Access Restriction | Open |
| Subject Keyword | Regulatory T Cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
