| First Author | Skadow M | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 2 | Pages | 370-378 |
| PubMed ID | 31167776 | Mgi Jnum | J:278404 |
| Mgi Id | MGI:6323730 | Doi | 10.4049/jimmunol.1900388 |
| Citation | Skadow M, et al. (2019) Helios Deficiency Predisposes the Differentiation of CD4(+)Foxp3(-) T Cells into Peripherally Derived Regulatory T Cells. J Immunol 203(2):370-378 |
| abstractText | The transcription factor Helios is expressed in a large percentage of Foxp3(+) regulatory T (Treg) cells and is required for the maintenance of their suppressive phenotype, as mice with a selective deficiency of Helios in Treg cells spontaneously develop autoimmunity. However, mice with a deficiency of Helios in all T cells do not exhibit autoimmunity, despite the defect in the suppressor function of their Treg cell population, suggesting that Helios also functions in non-Treg cells. Although Helios is expressed in a small subset of CD4(+)Foxp3(-) and CD8(+) T cells and its expression is upregulated upon T cell activation, its function in non-Treg cells remains unknown. To examine the function of Helios in CD4(+)Foxp3(-) T cells, we transferred Helios-sufficient or -deficient naive CD4(+)Foxp3(-) TCR transgenic T cells to normal recipients and examined their capacity to respond to their cognate Ag. Surprisingly, Helios-deficient CD4(+) T cells expanded and differentiated into Th1 or Th2 cytokine-producing effectors in a manner similar to wild-type TCR transgenic CD4(+) T cells. However, the primed Helios-deficient cells failed to expand upon secondary challenge with Ag. The tolerant state of the Helios-deficient memory T cells was not cell-intrinsic but was due to a small population of Helios-deficient naive T cells that had differentiated into Ag-specific peripheral Treg cells that suppressed the recall response in an Ag-specific manner. These findings demonstrate that Helios plays a role in the determination of CD4(+) T cell fate. |
