| Autor: |
Jhala, Gaurang, Krishnamurthy, Balasubramanian, Brodnicki, Thomas C., Ge, Tingting, Akazawa, Satoru, Selck, Claudia, Trivedi, Prerak M., Pappas, Evan G., Mackin, Leanne, Principe, Nicola, Brémaud, Erwan, De George, David J., Boon, Louis, Smyth, Ian, Chee, Jonathan, Kay, Thomas W.H., Thomas, Helen E. |
| Zdroj: |
Cell Reports; April 2022, Vol. 39 Issue: 4 |
| Abstrakt: |
Interferon gamma (IFNγ) is a proinflammatory cytokine implicated in autoimmune diseases. However, deficiency or neutralization of IFNγ is ineffective in reducing disease. We characterize islet antigen-specific T cells in non-obese diabetic (NOD) mice lacking all three IFN receptor genes. Diabetes is minimally affected, but at 125 days of age, antigen-specific CD8+T cells, quantified using major histocompatibility complex class I tetramers, are present in 10-fold greater numbers in Ifngr-mutant NOD mice. T cells from Ifngr-mutant mice have increased proliferative responses to interleukin-2 (IL-2). They also have reduced phosphorylated STAT1 and its target gene, suppressor of cytokine signaling 1 (SOCS-1). IFNγ controls the expansion of antigen-specific CD8+T cells by mechanisms which include increased SOCS-1 expression that regulates IL-2 signaling. The expanded CD8+T cells are likely to contribute to normal diabetes progression despite reduced inflammation in Ifngr-mutant mice. |
| Databáze: |
Supplemental Index |
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