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A two-hit model of autoimmunity: lymphopenia and unresponsiveness to TGF-β signaling

Cellular & Molecular Immunology volume 9, pages 369–370 (2012)Cite this article

The immune system can robustly respond to pathogens, while it is capable of maintaining tolerance to self and innocuous antigens, so that the body is not jeopardized by autoimmune reactivity. Under certain circumstances, nonetheless, control of homeostasis of the immune system is suspended, and the body subsequently fails to recognize its own constituent parts as self, which contributes to homeostatic peripheral expansion and autoimmune diseases. Although autoimmunity is extensively studied, the origins of this increasing public health challenge remain not well understood.

In the July issue of Nature Immunology, Zhang and Bevan revealed a novel perspective on the potential mechanisms of autoimmune disease and the control of lymphocyte homeostasis and tolerance.1 Their study provides new experimental support for the two-hit model of autoimmunity that has been previously proposed.2 By employing mouse models of T cell-specific conditional knockout of transforming growth factor-β (TGF-β) receptor (TGF-βRII), the authors demonstrated that the onset of autoimmune disease requires a trigger such as lymphopenia, but that this lymphopenia-driven autoimmunity can be inhibited by the action of TGF-β signaling on T cells.

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Authors and Affiliations

  1. Child Health Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ

    Andrew L'Huillier, Guangwen Ren, Yufang Shi & Jimin Zhang

  2. Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiaotong University School of Medicine, Shanghai, China

    Yufang Shi

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  1. Andrew L'Huillier
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  2. Guangwen Ren
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  3. Yufang Shi
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  4. Jimin Zhang
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Correspondence to Yufang Shi or Jimin Zhang.

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L'Huillier, A., Ren, G., Shi, Y. et al. A two-hit model of autoimmunity: lymphopenia and unresponsiveness to TGF-β signaling. Cell Mol Immunol 9, 369–370 (2012). https://doi.org/10.1038/cmi.2012.25

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