Artikel
IL-2 treatment reverses effects of CREM alpha overexpressing T cells in autoimmune prone mice
Suche in Medline nach
Autoren
Veröffentlicht: | 1. September 2015 |
---|
Gliederung
Text
Introduction: Systemic autoimmune diseases, like SLE are often characterized by a failure of self-tolerance and result in uncontrolled activation of B cells and effector T cells. IL-2 critically maintains homeostasis of regulatory T (Treg) cells and effector T cells in the periphery. Previously, we identified cAMP-responsive element modulator alpha (CREM alpha) as a major factor responsible for decreased IL-2 production in T cells from SLE patients. Additionally, using a transgenic mouse that specifically overexpresses CREM alpha in T cells (CD2CREMatg), we provided in vivo evidence that CREM alpha does indeed suppress IL-2 production.
Methods: To analyze the effects of CREM alpha in an autoimmune prone mouse model we introduced a Fas mutation in the CD2CREMatg mice and treated the mice with IL-2.
Results: Overexpression of CREM alpha strongly accelerated the already existing lymphadenopathy and splenomgaly in the FVB/Fas-/- mice. This was accompanied by a massive expansion of double negative (DN) T cells, enhanced numbers of IFN-y producing T cells and reduced percentages of Tregs. Treatment of FVB/Fas-/-CD2CREMatg mice with IL-2 restored the percentage of Tregs and reversed increased IFN-y production, but did not affect the number of DNTs.
Conclusion: Our data indicate that CREM alpha contributes to the failure of tolerance in SLE by favouring effector T cells and decreasing regulatory T cells, partially mediated by repression of IL-2 in vivo.