| First Author | Yang M | Year | 2018 |
| Journal | Immunology | Volume | 155 |
| Issue | 4 | Pages | 446-457 |
| PubMed ID | 29992549 | Mgi Jnum | J:267459 |
| Mgi Id | MGI:6256651 | Doi | 10.1111/imm.12983 |
| Citation | Yang M, et al. (2018) Regulatory T cells control epitope spreading in autoimmune arthritis independent of cytotoxic T-lymphocyte antigen-4. Immunology 155(4):446-457 |
| abstractText | CD4(+) Foxp3(+) regulatory T (Treg) cells can control both cellular and humoral immune responses; however, when and how Treg cells play a predominant role in regulating autoimmune disease remains elusive. To deplete Treg cells in vivo at given time-points, we used a mouse strain, susceptible to glucose-6-phosphate isomerase peptide-induced arthritis (GIA), in which the deletion of Treg cells can be controlled by diphtheria toxin treatment. By depleting Treg cells in the GIA mouse model, we found that a temporary lack of Treg cells at both priming and onset exaggerated disease development. Ablation of Treg cells led to the expansion of antigen-specific CD4(+) T cells including granulocyte-macrophage colony-stimulating factor, interferon-gamma and interleukin-17-producing T cells, and promoted both T-cell and B-cell epitope spreading, which perpetuated arthritis. Interestingly, specific depletion of cytotoxic T-lymphocyte antigen-4 (CTLA-4) on Treg cells only, was sufficient to protect mice from GIA, due to the expansion of CTLA-4(-) Treg cells expressing alternative suppressive molecules. Collectively, our findings suggest that Treg cells, independently of CTLA-4, act as the key driving force in controlling autoimmune arthritis development. |
