Peripheral blood follicular T cells. These cells are distinguished from conventional CD4+ T cells by the expression of CXCR5 and helper subsets categorized based on chemokine receptor, programmed death 1 (PD)‐1 and inducible T cell co‐stimulator (ICOS) expression. (a) Examining forkhead box protein 3 (FoxP3) and CXCR5 expression on live, single‐cell, CD3+CD4+ T cells reveals four distinct subsets (clockwise from top left quadrant): CCXR5–FoxP3+ regulatory T cells (Treg); CXCR5+FoxP3+ follicular T helper (Tfr); CXCR5+FoxP3– Tfh; and CXCR5–FoxP3– conventional T cells. The absence of CXCR5 fluorochrome‐conjugated antibody in Treg analysis would result in Tfr being analysed simultaneously with conventional Treg. Simultaneously, FoxP3 fluorochrome‐conjugated antibodies (or other regulatory markers) are required to distinguish between Tfh and follicular regulatory T (Tfr) cells. (b) CXCR5+FoxP3–CD45RA– Tfh cells can be categorized as Tfh17 (CCR6+CXCR3–), Tfh17.1 (CCR6+CXCR3+), Tfh1 (CCR6–CXCR3+) and Tfh2 (CCR6–CXCR3–). CCR4 and CD161 expression may be used to refine Tfh subsets further (refer to Table 1). (c) While helper capacity of Tfh1 cells is restricted to the activated ICOS+PD‐1++CCR7lo subset, all Tfh2 and Tfh17 cells are capable of helping B cells with varying capacity. The intensity of the background greyscale reflects the capacity to provide help to B cells. This figure has been adapted from reference
51 with permission from the authors.