For example, assessment of a cohort of common variable immunodeficiency (CVID) patients, including some with monogenic PIRDs, through flow and mass cytometry has revealed hallmarks of CD8+ T-cell exhaustion including co-expression of inhibitory receptors, loss of markers such as CD127 and CD28, and expression of transcriptional and epigenetic regulators such as TOX (61). The gene discussed is CD28; the disease is common variable immunodeficiency.