Repositioning TH cell polarization from single cytokines to complex help

When helper T (T-H) cell polarization was initially described three decades ago, the T-H cell universe grew dramatically. New subsets were described based on their expression of few specific cytokines. Beyond T(H)1 and T(H)2 cells, this led to the coining of various T(H)17 and regulatory (T-reg) cell subsets as well as T(H)22, T(H)25, follicular helper (T-FH), T(H)3, T(H)5 and T(H)9 cells. High-dimensional single-cell analysis revealed that a categorization of T-H cells into a single-cytokine-based nomenclature fails to capture the complexity and diversity of T-H cells. Similar to the simple nomenclature used to describe innate lymphoid cells (ILCs), we propose that T-H cell polarization should be categorized in terms of the help they provide to phagocytes (type 1), to B cells, eosinophils and mast cells (type 2) and to non-immune tissue cells, including the stroma and epithelium (type 3). Studying T-H cells based on their helper function and the cells they help, rather than phenotypic features such as individual analyzed cytokines or transcription factors, better captures T-H cell plasticity and conversion as well as the breadth of immune responses in vivo. The T helper subset paradigm has been instrumental in informing our understanding of T cell diversity; however, modern single-cell analyses have revealed the limits of the concept. In their Perspective, Becher and colleagues propose an alternative framework in which to understand T helper diversity, based not on transcription factors and cytokines but rather physiological functionality.

Automated summary

Three decades ago, the description of helper T cell polarization led to a dramatic growth in the T cell universe, with new subsets emerging. Categorizing T helper cells based on the help they provide offers a better understanding of their complexity and diversity.