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Enhanced CD28 signaling may be a common mechanism underlying resistance to regulation

Leukemia volume 21, page 175 (2007)Cite this article

We would like to point out a reference conspicuously omitted in an Original Article published online on 17 August 2006.

In this article, Loskog et al.1 report that the expression of a chimeric receptor that includes the intracellular portion of the CD28 receptor fused to the ζ-chain and CD19 single-chain Fv (CD19ζCD28) resulted in the resistance to regulation by regulatory T cells in a model of tumor rejection. Additionally, this complex also led to a significant increase in the threshold of responsiveness to the immunosuppressive cytokine transforming growth factor-β (TGF-β). The authors describe that the increased signaling through the CD28 pathway leads to an increase in T cell proliferation, an independence to IL-2, and enhanced nuclear factor-kappa B (NF-κB) activation, which is dependent on phosphatidylinositol 3-kinase (PI3K) activation. We reported in both 2004 and 2006 that mice deficient in Cbl-b, which have been shown to develop multiorgan inflammatory disease, have T-cell receptor (TCR) activation that is CD28-independent, and have T cell hyperactivation of the PI3K-Akt pathway, demonstrate resistance to suppression by both CD4+CD25+ regulatory T cells and TGF-β.2, 3 We termed this phenomenon ‘resistance to regulation’ in our 2004 article.2, 3

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References

  1. Loskog A, Giandomenico V, Rossig C, Dotti G, Brenner MK . Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. Leukemia (published online August 17, 2006; doi: 10.1038/sj.leu.2404366).

  2. Wohlfert EA, Callahan MK, Clark RB . Resistance to CD4+CD25+ regulatory T cells and TGF-beta in Cbl-b−/− mice. J Immunol 2004; 173: 1059–1065.

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  3. Wohlfert EA, Gorelik L, Mittler R, Flavell RA, Clark RB . Cutting Edge: Deficiency in the E3 ubiquitin ligase Cbl-b results in a multifunctional defect in T cell TGF-beta sensitivity in vitro and in vivo. J Immunol 2006; 176: 1316–1320.

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Authors and Affiliations

  1. Department of Immunology, Center of Immunotherapy for Cancer and Infectious Diseases, CT, Farmington, USA

    E A Wohlfert & R B Clark

  2. Division of Rheumatic Diseases, Department of Immunology, University of Connecticut Health Center, CT, Farmington, USA

    E A Wohlfert & R B Clark

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  1. E A Wohlfert
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  2. R B Clark
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Correspondence to R B Clark.

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Wohlfert, E., Clark, R. Enhanced CD28 signaling may be a common mechanism underlying resistance to regulation. Leukemia 21, 175 (2007). https://doi.org/10.1038/sj.leu.2404453

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