| First Author | Nyström SN | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 12 | Pages | 3621-31 |
| PubMed ID | 25231532 | Mgi Jnum | J:299326 |
| Mgi Id | MGI:6492361 | Doi | 10.1002/eji.201344432 |
| Citation | Nystrom SN, et al. (2014) Transient Treg-cell depletion in adult mice results in persistent self-reactive CD4(+) T-cell responses. Eur J Immunol 44(12):3621-31 |
| abstractText | Depletion of Foxp3(+) CD4(+) regulatory T cells (Treg) in adults results in chronic inflammation and autoimmune disease. However, the impact of transient Treg-cell depletion on self-reactive responses is poorly defined. Here, we studied the effect of transient depletion of Treg cells on CD4(+) T-cell responses to endogenous self-antigens. Short-term ablation of Treg cells in mice resulted in rapid activation of CD4(+) T cells, increased percentage of IFN-gamma(+) and Th17 cells in lymphoid organs, and development of autoimmune gastritis. To track self-reactive responses, we analyzed the activation of naive gastric-specific CD4(+) T cells. There was a dramatic increase in proliferation and acquisition of effector function of gastric-specific T cells in the stomach draining LNs of Treg-cell-depleted mice, compared with untreated mice, either during Treg-cell depletion or after Treg-cell reconstitution. Moreover, the hyperproliferation of gastric-specific T cells in the Treg-cell-ablated mice was predominantly antigen-dependent. Transient depletion of Treg cells resulted in a shift in the ratio of peripheral:thymic Treg cells in the reemerged Treg-cell population, indicating an altered composition of Treg cells. These findings indicate that transient Treg-cell depletion results in ongoing antigen-driven self-reactive T-cell responses and emphasize the continual requirement for an intact Treg-cell population. |
