Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus

Jens Y. Humrich, Henner Morbach, Reinmar Undeutsch, Philipp Enghard, Stefan Rosenberger, Olivia Weigert, Lutz Kloke, Juliane Heimann, Timo Gaber, Susan Brandenburg, Alexander Scheffold, Jochen Huehn, Andreas Radbruch, Gerd Rüdiger Burmester, Gabriela Riemekasten

98 Citations (Scopus)


The origins and consequences of a regulatory T cell (Treg) disorder in systemic lupus erythematosus (SLE) are poorly understood. In the (NZBxNZW) F1 mouse model of lupus, we found that CD4+Foxp3 + Treg failed to maintain a competitive pool size in the peripheral lymphoid organs resulting in a progressive homeostatic imbalance of CD4 +Foxp3+ Treg and CD4+Foxp3- conventional T cells (Tcon). In addition, Treg acquired phenotypic changes that are reminiscent of IL-2 deficiency concomitantly to a progressive decline in IL-2-producing Tcon and an increase in activated, IFN-γ-producing effector Tcon. Nonetheless, Treg from lupusprone mice were functionally intact and capable to influence the course of disease. Systemic reduction of IL-2 levels early in disease promoted Tcon hyperactivity, induced the imbalance of Treg and effector Tcon, and strongly accelerated disease progression. In contrast, administration of IL-2 partially restored the balance of Treg and effector Tcon by promoting the homeostatic proliferation of endogenous Treg and impeded the progression of established disease. Thus, an acquired and self-amplifying disruption of the Treg-IL-2 axis contributed essentially to Tcon hyperactivity and the development of murine lupus. The reversibility of this homeostatic Treg disorder provides promising approaches for the treatment of SLE.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
Pages (from-to)204-209
Number of pages6
Publication statusPublished - 2010

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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