Differences in TIGIT⁺ T_FH activity between alloimmunized and nonalloimmunized SCD patients. Our data suggest that alloimmunized patients with SCD have comparable levels of TIGIT and frequency of TIGIT⁺ T_FH cells as nonalloimmunized SCD patients. However, functional activity of TIGIT⁺ T_FH cells differs between the 2 groups: TIGIT⁺ T_FH cells from nonalloimmunized SCD patients express less B-cell costimulatory markers such as Inducible T-cell COStimulator (ICOS) and CD40 ligand (CD40L) and produce less IL-21, which we hypothesize is due to differences in TIGIT signaling between the 2 groups. As a result, these cells from nonalloimmunized SCD patients are less effective in providing help to B cells to produce IgG compared with alloimmunized SCD patients who have more potent TIGIT⁺ T_FH cells.