| First Author | Humblet-Baron S | Year | 2007 |
| Journal | J Clin Invest | Volume | 117 |
| Issue | 2 | Pages | 407-18 |
| PubMed ID | 17218989 | Mgi Jnum | J:117933 |
| Mgi Id | MGI:3698073 | Doi | 10.1172/JCI29539 |
| Citation | Humblet-Baron S, et al. (2007) Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis. J Clin Invest 117(2):407-418 |
| abstractText | Wiskott-Aldrich syndrome protein (WASp) is essential for optimal T cell activation. Patients with WAS exhibit both immunodeficiency and a marked susceptibility to systemic autoimmunity. We investigated whether alterations in Treg function might explain these paradoxical observations. While WASp-deficient (WASp(-/-)) mice exhibited normal thymic Treg generation, the competitive fitness of peripheral Tregs was severely compromised. The total percentage of forkhead box P3-positive (Foxp3(+)) Tregs among CD4(+) T cells was reduced, and WASp(-/-) Tregs were rapidly outcompeted by WASp(+) Tregs in vivo. These findings correlated with reduced expression of markers associated with self-antigen-driven peripheral Treg activation and homing to inflamed tissue. Consistent with these findings, WASp(-/-) Tregs showed a reduced ability to control aberrant T cell activation and autoimmune pathology in Foxp3(-/-)Scurfy (sf) mice. Finally, WASp(+) Tregs exhibited a marked selective advantage in vivo in a WAS patient with a spontaneous revertant mutation, indicating that altered Treg fitness likely explains the autoimmune features in human WAS. |
