Targeting TFH cells in human diseases and vaccination: rationale and practice

Yu et al. review the roles played by follicular helper T cells in sustaining germinal center B cell responses and vaccination strategies, as well as potential pathogenic autoimmune responses. The identification of CD4(+) T cells localizing to B cell follicles has revolutionized the knowledge of how humoral immunity is generated. Follicular helper T (T-FH) cells support germinal center (GC) formation and regulate clonal selection and differentiation of memory and antibody-secreting B cells, thus controlling antibody affinity maturation and memory. T-FH cells are essential in sustaining protective antibody responses necessary for pathogen clearance in infection and vaccine-mediated protection. Conversely, aberrant and excessive T-FH cell responses mediate and sustain pathogenic antibodies to autoantigens, alloantigens, and allergens, facilitate lymphomagenesis, and even harbor viral reservoirs. T-FH cell generation and function are determined by T cell antigen receptor (TCR), costimulation, and cytokine signals, together with specific metabolic and survival mechanisms. Such regulation is crucial to understanding disease pathogenesis and informing the development of emerging therapies for disease or novel approaches to boost vaccine efficacy.

Automated summary

Yu et al. review the crucial roles of follicular helper T cells in humoral immunity, including sustaining germinal center B cell responses, regulating antibody affinity maturation and memory formation, and mediating pathogenic autoimmune responses. Understanding the regulation of follicular helper T cell generation and function is important for disease prevention and treatment, as well as vaccine development and enhancement.