Trends in Immunology
ReviewCytokine-skewed Tfh cells: functional consequences for B cell help
Highlights
The inflammatory environment and the cytokine milieu induce T follicular helper (Tfh) cells to differentiate into different subsets that pertain to type 1 inflammatory responses (Tfh1), type 2 inflammatory responses (Tfh2), and T regulatory responses (Tfr), as well as the production of interleukin (IL)-17 (Tfh17) cells with varying capacity to provide help to B cells in mammals.
Cytokine-skewed Tfh cells contribute to class-switch recombination before germinal center (GC) formation and modify B cell maturation within GCs.
The accessibility in conventional Tfh cells of specific gene loci typical of CD4+ T helper cells through epigenetic programming might facilitate their transition into Tfh1, Tfh2, Tfh17, or Tfr phenotypes.
The heterogeneity of Tfh cells underscores their ability to modulate different humoral immune responses to different pathogens, all with varying consequences. For instance, production of interferon (IFN)-γ by Tfh1 cells can impair B cell function during Plasmodium sp. infection but enhances B cell function in some viral infections.
Cytokines produced by Tfh2/Tfh13 cells can mediate not only antibody class switching but also the affinity of the IgE produced.
The suppressive activity of Tfr cells depends on their origin, as well as on their location.
CD4+ follicular helper T (Tfh) cells play a vital role in providing help for B cells undergoing selection and differentiation into activated antibody-secreting cells in mammalian germinal centers (GCs). Increasing evidence suggests that Tfh cells are a heterogeneous population that generates cytokine-skewed immune responses – a reflection of the microenvironment during differentiation. This has important ramifications for Tfh-mediated B cell help. Because Tfh subsets can have opposing effects on GC B cell responses, we discuss current findings regarding the differentiation and functions of cytokine-skewed Tfh cells in modulating GC B cell differentiation. Antibodies are important weapons against infectious diseases but can also be pathogenic mediators in some autoimmune conditions. Since cytokine-skewed Tfh cells can influence the magnitude and quality of the humoral response, we address the roles of cytokine-skewed Tfh cells in disease.