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A complex issue on CD4+ T‐cell subsets

This article introduces a series of reviews covering CD4 T-cell Subsets appearing in Volume 252 of Immunological Reviews. CD4 T-cell-mediated immune responses are instrumental to eliminate viral, bacterial, fungal, or parasitic infections or malignant cells through secretion of cytokines and activation and recruitment of macrophages, neutrophils, eosinophils, and basophils. CD4 T cells also provide help for B cells to make antibodies. CD4 T-cell-mediated immunity can also involve aberrant recognition of autoantigens, leading to autoimmune diseases. CD4 regulatory T cells (Tregs) play a central role in the control of autoimmunity, immune homeostasis, and immune responses to pathogens and tumor antigens. We now appreciate that several subsets of CD4 T cells exist that shape the adaptive immune responses. In the 1980s and 1990s, two seminal discoveries defined the biology of CD4 T-cell subsets: the concept of the T-helper 1 (Th1)/Th2 paradigm and the identification of CD4CD25 Tregs. Since the beginning of new millennium, immunologists have made great strides in our understanding of the immunobiology of CD4 T cells, and consequently more CD4 T-cell subsets have been identified, namely Th17, Th9, and Th22 cells. Together with the re-appreciation of follicular T-helper cells (Tfh) which were first observed in the 1970s, we now understand that the CD4 T-cell subsets play roles in adaptive immunity ranging from the clearance of pathogens and the control of autoimmunity to immune homeostasis and immune responses again tumors (Fig. 1). Herein, we introduce CD4 T-cell subsets and provide a snapshot of this volume of Immunological Reviews, which updates this rapidly advancing area of immunology that covers diverse aspects of CD4 T-cell subsets including molecular control of its development and lineage plasticity, function in immunological diseases, and clinical application.