Interleukin-2 independent expansion of Helios-expressing T-cells contributes to autoimmunity in regulatory T-cell deficient mice (115.13)
| Autor: | Rahul Sharma, Christian Abaya, Chiao-Ying Ju, Shyr-Te Ju |
|---|---|
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:115.13-115.13 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The CD4+Foxp3+ T regulatory cells (Treg) are important for peripheral tolerance. Expression of the transcription factor Helios (Hel) was recently identified as a marker for thymus-derived Treg (tTreg), and was not expressed on the induced Treg. A minor population of CD4+Foxp3negHel+ T-cells is present in normal B6 mice. We hypothesized that this population may be related to tTreg in lineage and may contribute to autoimmunity during lack of Foxp3 expression. Indeed, in Treg deficient Il2-/- and Scurfy (Sf) mice, the CD4+Foxp3negHel+ T-cells expanded in the periphery. These cells produced high levels of inflammatory cytokines and were present at high numbers in the inflamed organs. The peripheral maintenance of the CD4+Foxp3negHel+ cells was independent of interleukin (IL)-2 because they expanded in the periphery of Il2-/- and IL-2 deficient Sf mice (Sf.Il2-/- mice). In this respect, the majority of the peripheral Treg in the Il2-/- mice are Hel+, suggesting that they are also relatively IL-2 independent. Importantly, abnormal Foxp3 mRNA could be detected in the Sf CD4+ T-cells that contain high percentage of Hel+ T-cells. The data strongly suggest that abnormal tTreg contribute significantly to the CD4+Foxp3negHel+ T-cell -mediated autoimmunity in Sf mice. In contrast to Treg, the expansion of CD4+Foxp3negHel+ T-cells becomes IL-2 independent |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|