Follicular Helper T Cells in Immunity and Autoimmunity

T follicular helper cells (Tfh) are professional B cell helper cells in germinal centers (GCs), lymphoid structures where B cell maturation into high affinity plasma cells and memory B cells takes place. Upon antigen encounter, a fraction of T cells upregulates chemokine receptor CXCR5 that allows their locali-zation inside the B cell follicles where together with dendritic cells and B cells initiate the GC response. These CXCR5-expressing T cells upregulate Bcl-6, acquire the full differentiation program of the Tfh cell lineage, and help B cells undergo class switch recombination and somatic hypermutation through the expression of co-stimulatory molecules and the secretion of cytokines. Tfh cells can be found in circula-tion and recent studies have identified multiple Tfh subsets based on the expression of chemokine re-ceptors and activation molecules. The distribution of circulating Tfh subsets, their number and activa-tion phenotype have been associated with the clinical outcome of numerous diseases spanning from autoimmunity to immunodeficiency and were shown to correlate with responses to infections and vac-cines. Circulating Tfh cells are thought to represent events that take place in tissues and lymphoid or-gans. However, the differentiation and plasticity of Tfh subsets, the functional consequences of Tfh in-teraction with B cells outside GCs such as in the tissues and the mechanisms that determine the impact of Tfh on B cell activation and differentiation are largely undetermined. A population of FOXP3+ regula-tory T cells that expresses CXCR5 and controls GC responses was recently described. However, the fac-tors that control their generation and the mechanisms of suppression are poorly understood. Tfh and Tfr are currently being used as biomarkers and therapeutic targets in various clinical settings, including cancer and transplantation. A clear understanding of the mechanisms that control the development of Tfh and Tfr and the factors that contribute to GC responses is vital to the success of Tfh-based im-mune-monitoring and therapy development.

This Research Topic aims at addressing these questions with the final aim to better understand the bi-ology of Tfh and how these cells could be targeted to harness undesired immune responses or boost immunity. We seek articles that cover, but are not limited to, the following topics:

1. Lineage specification of Tfh subsets and their function
2. Molecular control of Tfh development and differentiation
3. T-cell extrinsic signals that control Tfh development
4. Regulation of GC responses by Tfr cells
5. Tfh in infections
6. Tfh in vaccine response
7. Tfh in antiviral immunity
8. Tfh in autoimmune disorders
9. Tfh in primary immunodeficiencies
10. Tfh in transplantation tolerance
11. TFR in cancer
11. TFR in immune response changes in aging
12. Biomarker development and therapeutic targeting of Tfh