Recovery from experimental allergic encephalomyelitis is TGF-β dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells
| Autor: | Howard L. Weiner, Hirofumi Ochi, Dan Frenkel, Xingmin Zhang, Jayagopala Reddy, Vijay K. Kuchroo |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Encephalomyelitis Autoimmune Experimental Proteolipid protein 1 Encephalomyelitis Immunology Enzyme-Linked Immunosorbent Assay chemical and pharmacologic phenomena Spleen Mice Transforming Growth Factor beta immune system diseases medicine Animals Immunology and Allergy IL-2 receptor Receptor Lymph node biology Reverse Transcriptase Polymerase Chain Reaction CCAAT-Enhancer-Binding Protein-beta Forkhead Transcription Factors Receptors Interleukin-2 Recovery of Function General Medicine Flow Cytometry medicine.disease Adoptive Transfer Molecular biology nervous system diseases medicine.anatomical_structure biology.protein Female Antibody |
| Zdroj: | International Immunology. 18:495-503 |
| ISSN: | 1460-2377 0953-8178 |
| DOI: | 10.1093/intimm/dxh390 |
| Popis: | SJL mice are highly susceptible to proteolipid protein (PLP) 139-151-induced experimental allergic encephalomyelitis (EAE). The disease is characterized by a relapsing-remitting type of paralysis. However, the mechanism by which animals recover from EAE is poorly understood. Here, we investigated the role of regulatory T cells in the recovery from disease. We found that Forkhead box P3-expressing CD4+CD25+ T cells were increased in the blood, draining lymph node and spleen of EAE-recovered SJL mice. These cells were anergic and inhibited proliferation of CD4+CD25- T cells to PLP 139-151 or anti-CD3 antibody stimulation. Depletion of CD4+CD25+ T cells during the recovery phase exacerbated disease, resulted in the expansion of IA(s)/PLP 139-151-tetramer-positive cells and enhanced IFN-gamma production. In addition, transforming growth factor-beta (TGF-beta) was shown to be involved in the recovery from EAE as the percentage of CD4+ cells expressing TGF-beta latency-associated peptide (LAP) on the cell surface increased significantly in blood and spleen of EAE-recovered mice as compared with the naive mice and in vivo neutralization of TGF-beta abolished recovery from disease. Taken together, our results demonstrate that both CD4+CD25+ and CD4+LAP+ regulatory T cells mediate recovery from PLP 139-151-induced EAE in SJL mice in which TGF-beta plays an important role. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|