Phenotype and functions of memory Tfh cells in human blood

• CXCR5+ CD4+ T cells represent a circulating memory compartment of Tfh lineage cells.
• Blood memory Tfh cells are composed of phenotypically and functionally distinct subsets.
• A proposed 3D approach defines nine blood memory Tfh subsets.

Our understanding of the origin and functions of human blood CXCR5+ CD4+ T cells found in human blood has changed dramatically in the past years. These cells are currently considered to represent a circulating memory compartment of T follicular helper (Tfh) lineage cells. Recent studies have shown that blood memory Tfh cells are composed of phenotypically and functionally distinct subsets. Here, we review the current understanding of human blood memory Tfh cells and the subsets within this compartment. We present a strategy to define these subsets based on cell surface profiles. Finally, we discuss how increased understanding of the biology of blood memory Tfh cells may contribute insight into the pathogenesis of autoimmune diseases and the mode of action of vaccines.