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Tracking Tolerance—T Regulatory Type 1 Cell Markers Revealed

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Science Translational Medicine  29 May 2013:
Vol. 5, Issue 187, pp. 187ec91
DOI: 10.1126/scitranslmed.3006581

“With great power comes great responsibility.” Scientists have long sought to understand how Voltaire’s edict applies to the immune system. Unchecked, immune cells can run amuck, attacking the body’s own cells, leading to autoimmune disease. One mechanism with which the immune system behaves responsibly is through a group of suppressive immune cell types known collectively as regulatory T cells (Treg cells). Treg cells are crucial for the maintenance of self-tolerance, and different types of Treg cells have specialized functions. For example, type 1 regulatory T cells (Tr1) are able to kill myeloid antigen-presenting cells and also express high levels of the immunosuppressive cytokine interleukin 10 (IL-10). However, understanding the role of these potent anti-inflammatory cells has heretofore been hampered by the lack of phenotypic markers to count and track these cells in various experimental and clinical settings.

In a recent edition of Nature Medicine, Gagliani and colleagues describe the phenotypic characterization of Tr1 cells using the cell-surface markers CD49b and LAG-3. They first performed gene expression profiling on T cell clones derived from human subjects so as to identify T cell markers differentially expressed in Tr1 compared with naïve CD4+ T cells. Genes specific to the Tr1 clones included CD49b and LAG-3. Using flow cytometry of peripheral blood samples from humans and mice, these two markers were used to define a subpopulation of CD4+ T cells capable of high IL-10 expression and suppression of T cell proliferation in vitro and in vivo. Moreover, adoptive transfer of CD4+ CD49b+ LAG-3+ cells was sufficient for the suppression of autoimmune disease activity in vivo by using a mouse model of autoimmune colitis. Furthermore, increased percentages of memory CD4 cells coexpressing CD49b and LAG-3 were observed in patients with persistent mixed chimerism after allogenic hematopoietic stem cell transplantation for β-thallassemia, suggesting that these markers may correlate with greater immune tolerance in humans.

This study paves the way for additional study of Tr1 cells in a variety of clinical and experimental settings. Ultimately, this study may also make the isolation of these cells feasible, leading to novel lines of therapeutic investigation in transplantation, oncology, and autoimmune diseases.

N. Gagliani et al., Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med 28 April 2013 (10.1038/nm.317) [Abstract]

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