Persons with SCD have increased circulating iNKT cells that express activation markers. Fluorescently labeled CD1d tetramers were used to selectively label iNKT cells (defined as tetramer⁺ CD3⁺) in the blood of persons with SCD (HbSS) and appropriate age- and race-matched controls. (A) Representative flow cytometry plots of circulating human iNKT cells. (B) iNKT cells were identified from the live, CD45⁺ lymphocyte gate as CD1d-tetramer⁺ CD3⁺ cells. Compared with controls, persons with SCD have a higher number of circulating iNKT cells. (C-D) iNKT cells from persons with SCD are more activated as defined by higher percentage of surface CD69 and CXCR3 and intracellular IFN-γ. Data were analyzed by an unpaired Student t test. SSC indicates side scatter.