| First Author | Franckaert D | Year | 2015 |
| Journal | Immunol Cell Biol | Volume | 93 |
| Issue | 4 | Pages | 417-23 |
| PubMed ID | 25533288 | Mgi Jnum | J:232694 |
| Mgi Id | MGI:5779802 | Doi | 10.1038/icb.2014.108 |
| Citation | Franckaert D, et al. (2015) Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3(+) and Foxp3(-) T cells. Immunol Cell Biol 93(4):417-23 |
| abstractText | Costimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to mice bearing a conditional Cd28 allele. Treg-specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantage in competitive fitness and proliferation of CD28-deficient Tregs. By contrast, Treg survival and lineage integrity were not affected by the lack of CD28. This data demonstrate that, even after the initial induction requirement, Treg maintain a higher dependency on CD28 signalling than conventional T cells for homeostasis. In addition, we found the Foxp3-CreYFP allele to be a hypomorph, with reduced Foxp3 protein levels. Furthermore, we report here the stochastic activity of the Foxp3-CreYFP allele in non-Tregs, sufficient to recombine some conditional alleles (including Cd28) but not others (including R26-RFP). This hypomorphism and 'leaky' expression of the Foxp3-CreYFP allele should be considered when analysing the conditionally mutated Treg. |
