Regulatory T cells: recommendations to simplify the nomenclature

By A. Abbas, C. Benoist, J. Bluestone, D. Campbell, S. Ghosh, S. Hori, Shuiping Jiang, V. Kuchroo, D. Mathis, M. Roncarolo and 5 more. Nature Immunology, 2013

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c o rr e s p o n d e n c e npg © 2013 Nature America, Inc. All rights reserved. Regulatory T cells: recommendations to simplify the nomenclature To the Editor: Regulatory T cells (T reg cells) have attracted much interest from both basic and clinical immunologists. Although questions remain about their fundamental biology and their clinical potential has yet to be fully realized, considerable advances have been made in the under- standing of the differentiation, homeostasis and function of T reg cells. This new knowledge has led to a substantial increase in the number of Foxp3 + T reg cell subpopulations described in the literature and conse- quently to an increase in the use of new abbreviations and terminology. Furthermore, as the understanding of T reg cell biology has grown, so too has the realization that some aspects of the original terminology are no longer accurate, and its use has become less stringent. At the Third International Conference on Regulatory T Cells and Th Subsets and Clinical Application in Human Diseases held in Shanghai, China, on 13–16 October 2012, a small workshop was convened to discuss T reg cell nomenclature and to develop several recommendations. We hasten to add that this is simply a list of recommendations, and it remains the prerogative of journals to develop their own editorial preferences and for the authors to use the nomenclature they feel best suits their manuscript. However, we support the recommendations noted below. There were three general issues that provided the momentum for this workshop. First, the terms used for the principal Foxp3 + T reg cell populations—those that differentiate in the thymus, those that differ- entiate in the periphery and those generated in vitro—are not ideal, as these are, to some extent, inaccurate, ambiguous and/or uninformative. For example, the widely used term ‘natural T reg cell’ is misleading and ambiguous, as it indicates that all other Foxp3 + T reg cell populations are ‘unnatural’. It also does not convey any useful or accurate information. One feature of these Foxp3 + T reg cell populations that is more informa- tive is the anatomical location of their differentiation. Instead, use of the terms ‘thymus’, ‘periphery’ and ‘in vitro’ provides a clear indica- tion of whence the Foxp3 + T reg cells in question are derived. Thus, we would recommend that ‘natural Foxp3 + T reg cells’ instead be referred to as ‘thymus-derived T reg cells’ (Box 1). Consistent with the rationale above, we would recommend that Foxp3 + T reg cells that differentiate in the periphery be referred to as ‘peripherally derived T reg cells’ rather than ‘induced or adaptive T reg cells’ (Box 1). In this context, we noted that terms used to define a T reg cell subpopulation, such as ‘induced T reg cells’, are often used when the location of their differentiation is unclear. Thus, we would suggest that the newly recommended terms ‘thymus-derived T reg cells’ and ‘peripherally derived T reg cells’ be used only when the anatomical location of their differentiation has been clearly demonstrated. When the origin of the T reg cell being studied is unclear, the general term ‘Foxp3 + T reg cell’ would be more appropriate. Finally, to clearly distinguish between Foxp3 + T reg cell populations that are generated in vivo versus those generated in vitro, we would suggest nature immunology volume 14 number 4 april 2013 that the term ‘in vitro–induced T reg cells’ be used for all Foxp3 + T reg cell populations generated ex vivo, such as those generated through the use of transforming growth factor-b (Box 1). Second, there has been a growing tendency to use terms such as ‘T reg cells’ or ‘iT reg cells’ when confirmation of such identity is lacking. The frequent use of the term ‘T reg cells’ has been a particular problem in studies focusing on human T reg cells, as activated conventional T cells can also express Foxp3. The term ‘T reg cell’ should be used only when it is clear that the cells have (or had) suppressive ability or have a transcriptional, epigenetic and/or protein-expression signature that suggests that the cells in question are, beyond a reasonable doubt, Foxp3 + T reg cells (Box 1). Also, as indicated above, the terms ‘thymus- derived T reg cell’ and ‘peripherally derived T reg cells’ should be used only when the anatomical location of their development has been clearly demonstrated. Third, there has been progressive growth in the development and use of new T reg cell terminology that is likely to lead to more confusion and the further ‘jargonization’ of immunology. Until a new popula- tion has been extensively demonstrated to be unique, distinct from other populations and stable, we would recommend not coining new terms for such subpopulations (Box 1). Instead, we would encourage investigators to identify them through the use of prominent aspects of their expression pattern, such as a transcription factor or cytokine. Although the focus of this Correspondence has been CD4 + Foxp3 + T reg cell populations, many CD4 – Foxp3 – T reg cell populations have been described, and we would similarly recommend that new terms be used to describe these only when their identity and stability have been clearly defined. Box 1 T reg cell nomenclature recommendations 1. ‘Thymus-derived T reg cell (tT reg cell)’ should be used instead of ‘natural T reg cell (nT reg cell)’. 2. ‘Peripherally derived T reg cell (pT reg cell)’ should be used instead of ‘induced or adaptive T reg cell (iT reg cell or aT reg cell)’. 3. ‘In vitro–induced T reg cell (iT reg cell)’ should be used to clearly distinguish between those T reg cell populations generated in vivo versus those generated in vitro. 4. T reg cell terms should be used only when there is definitive evidence justifying their use. 5. The development and use of new T reg cell terminology should be limited, especially for subpopulations.

Subfields: Immunology

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