Guidelines for T cell nomenclature, 2025, Masopust et al.

[SNT Gatchaman]

Guidelines for T cell nomenclature

Spoiler: Authors

Masopust, David; Awasthi, Amit; Bosselut, Rémy; Brooks, David G; Buggert, Marcus; Chamoto, Kenji; Cui, Weiguo; Dong, Chen; Farber, Donna L; Gebhardt, Thomas; Gerlach, Carmen; Goldrath, Ananda; Greenberg, Philip D; Hale, J Scott; Hayday, Adrian; Homann, Dirk; Iannacone, Matteo; Jameson, Stephen C; Jenkins, Marc K; Joshi, Nikhil S; Kaech, Susan M; Kallies, Axel; Kamphorst, Alice O; Kaplan, Mark H; Klenerman, Paul; Künzli, Marco; Lanzavecchia, Antonio; Lauer, Georg M; Lugli, Enrico; Luster, Andrew D; Mackay, Laura K; McElrath, M Juliana; Mueller, Scott N; Ndhlovu, Zaza; Ndung’u, Thumbi; Ohashi, Pamela S; Oxenius, Annette; Pantaleo, Giuseppe; Pepper, Marion; Picker, Louis J; Quarnstrom, Clare F; Reyes-Terán, Gustavo; Roederer, Mario; Rosato, Pamela C; de Oca, Gonzalo Salgado-Montes; Sallusto, Federica; Schumacher, Ton N; Schwartz, Daniella M; Shin, Eui-Cheol; Soerens, Andrew G; Thommen, Daniela S; Vezys, Vaiva; Viola, João P B; Walker, Bruce D; Watts, Tania H; Weaver, Casey T; Wherry, E John; Xue, Hai-Hui; Youngblood, Ben; Ahmed, Rafi

Advances in T cell biology have revealed heterogeneity among T cell populations that is not captured by existing general nomenclature. This issue has caused an ad hoc broadening of core T cell subset definitions and the invention of new subset designations that have not been uniformly delineated.

To address this issue, in this Consensus Statement, we propose guidelines that serve three goals. First, they advocate that primary research reports define the experimental basis by which relevant subsets are designated in the methods section of each study. Second, they provide standardized definitions for existing subset designations in popular use, and common experimental criteria for defining each subset are noted. Last, they present an alternative ‘modular nomenclature’ paradigm.

The newly proposed modular nomenclature eschews conceptualization of antigen-experienced T cells as belonging to a few idealized subsets, and the nomenclature instead simply indicates individual biological properties present in a T cell population with brief descriptors.

Collectively, these guidelines intend to enhance transparency in the literature while facilitating clearer communication of findings and concepts to researchers, students and clinicians.

Web | DOI | PDF | Nature Reviews Immunology | Open Access

 

[SNT Gatchaman]

Posting for reference.

The advent of four-colour flow cytometry in the 1990s drew attention to heterogeneity among memory-phenotype T cells. Two terms, central memory T (TCM) cell and effector memory T (TEM) cell, gained traction, and both the molecular and biological definitions of these terms quickly evolved. TCM cell and TEM cell designations were correlated with the expression of lymph node-homing receptors (typically CC-chemokine receptor 7 (CCR7) in humans and L-selectin (CD62L) in mice), isoform expression of the CD45 protein tyrosine phosphatase in humans (CD45RO or CD45RA), or patterns of expression of Fas death receptor (CD95) and a co-stimulatory receptor (CD28) in non-human primates. In other words, synonymous subsets (also referred to as ‘lineages’) were defined by different markers in each species, and these markers were collectively interpreted to correlate with a broad range of biological properties.

To complicate matters, specifically in humans, the popular term TEMRA (T effector memory re-expressing CD45RA) was also coined to describe those CD8+ ‘TEM cells’ that were CD45RA+. In practice, TCM and TEM cell subsetting lumped the properties of migration, function, proliferation and differentiation potential together, although some investigators favoured one property over another.

The TCM/TEM paradigm coincided with increasing evidence that CD4+ T cells adopted functional specializations, leading to the classification of T helper 1 (TH1), T helper 2 (TH2), regulatory T (Treg), T helper 9 (TH9), T helper 17 (TH17) and follicular helper T (TFH) cells and an increasing subsetting of subsets (for example, germinal centre TFH (GC TFH) cells versus effector TFH cells, or numerous flavours of Treg cells) using approaches that did not collectively address the migration, proliferation and differentiation potential of the T cell populations.

Memory T cells in non-lymphoid tissues that, one, lack expression of lymph node-homing molecules and, two, execute rapid effector functions were originally included in the TEM vernacular. However, because considerable evidence indicated that most of these cells do not recirculate through blood, they were subsequently renamed resident memory T (TRM) cells, rather than being designated as a ‘subset’ of TEM cells, to prioritize this migratory property.

The persistence of antigen has profound effects on T cell differentiation. This variable was not well-captured in the original T cell nomenclature, and the term ‘memory’ was (and still is) often used to refer to T cells specific for pathogens causing both acutely resolved and chronic infections. However, the term ‘exhaustion’ (and several related terms) was coined to describe the hypofunctional T cells that predominate in some settings of chronic infections and cancer. Exhausted T (TEX) cell subsets embody both migratory and resident T cell populations and include terminally differentiated T cells, T cells that retain proliferation and differentiation potential, and T cells that lie somewhere between these extremes. Many other T cell subset definitions have been coined that relate to differentiation potential and longevity, including stem cell memory T (TSCM) cells, memory precursor effector cells (MPECs), short-lived effector cells (SLECs), and long-lived effector cells (LLECs), to name but a few.

The issue is that as we have learned more, it has become obvious that T cells exhibit diversity in migration, function, proliferation and differentiation potential, as well as in more difficult-to-measure qualities, including longevity and their potency to affect particular immune responses, such as pathogen control. Because these properties are not always co-regulated, a limited vocabulary of subsets will intrinsically fail to capture all relevant biological properties. This has resulted in an ad hoc expansion of the T cell nomenclature that has proceeded organically, without a top–down reorganization that benefits from the combined state of current knowledge.

 

[Jonathan Edwards]

"The issue is that as we have learned more, it has become obvious that T cells exhibit diversity in migration, function, proliferation and differentiation potential, as well as in more difficult-to-measure qualities, including longevity and their potency to affect particular immune responses, such as pathogen control. Because these properties are not always co-regulated, a limited vocabulary of subsets will intrinsically fail to capture all relevant biological properties."

Some of us were saying this in the 1980s. Recognition of the reality is long overdue