Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4(+)CD28(null) T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4(+)CD28(null) T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4(+)CD28(null) T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4(+)CD28(null) T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4(+)CD28(null) T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4(+)CD28(null) T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4(+)CD28(null) T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.