Responsible for mobilizing innate cells; providing help to B cells for class switching

and antigen-specific immunoglobulin production; providing cues to local tissue and promoting wound healing and repair, CD4+ Th cells are fully operational conductors of immune activation, resolution and tissue repair. With such influence, CD4+ Th cells are tightly regulated throughout their development from the bone marrow, liver and thymus, through to their peripheral differentiation, activation, effector function and long-term survival. Despite multiple checkpoints and layers of highly evolved immune regulation, CD4+ Th cell dysfunction can arise, leading to hyper-inflammatory conditions causing local tissue damage and culminating in autoimmune or allergic diseases. Conversely, if CD4+ Th cells

fail to develop, mature or differentiate, Osimertinib clinical trial individuals can be left with insufficient immunological protection with equally catastrophic outcomes, such as life-threatening severe immunodeficiency. Relatively unchallenged for almost 20 years, it was widely accepted that CD4+ Th cells differentiate into two distinct effector populations, interferon-γ (IFN-γ)-producing Th1 cells and interleukin-4 (IL-4) -producing Th2 cells.1 It is now customary to acknowledge at least five, if not six, CD4+ T-cell subsets including Th1, Th2, Th17, T follicular helper (T Fh) and regulatory T (Treg) cells plus the yet to be fully accepted at the time of print Th9 cells.2,3 With the exception of T Fh and Treg cells, click here effector CD4+ Th subsets are characterized by their cytokine expression profile and up-stream transcription factor usage. Beyond the usefulness for communication among scientists, pigeonholing T cells into such categories may be over-simplifying Th cell biology. Resveratrol The initial description of Th1 and Th2 cells described the outgrowth of irreversibly committed IFN-γ-producing or IL-4-producing T-cell clones over several weeks, a bench mark yet to be met for Th17 or Th9 cells. Plasticity between the subsets is widely documented (reviewed by Murphy and Stockinger4) with studies identifying Th2 (GATA3+ IL-4+) cells that co-express

Th1 (T-bet and IFN-γ) -defining,5 Th17 (RoRγt and IL-17A) -defining6 markers or IL-9-secretion3 (Fig. 1). Despite the potential shortcomings of these studies (using in vitro-polarized or transgenic T-cell systems) these observations throw into question the biological and physiological relevance of subsets – Th1, Th2, and ‘Th2+1’ or ‘IL-17–Th2’ as the authors justly deride. Nevertheless, for the benefit of communication and until a more useful system is established, throughout this review we will subscribe to the current nomenclature and tie together recent advances in our understanding of Th2 cells, highlighting where possible the unique features of Th2 cells. Widely cited as being required for anti-helminth immunity, Th2 cells have only clearly been demonstrated to expel intestinal helminth infections.