Exogenous interleukin-2 can rescue in-vitro T cell activation and proliferation in patients with a novel CARMIL2 mutation.

Capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is characterized by impaired T cell activation, which is attributed to defective CD28-mediated co-signaling. Herein, we aimed to analyze the effect of exogenous interleukin (IL)-2 on in-vitro T cell activation and proliferation in a family with CARMIL2 deficiency. This study included four children (one male and three females; 2.5-10 years old at presentation). The patients presented with inflammatory bowel disease and recurrent viral infections. Genetic analysis revealed a novel homozygous 25-bp deletion in CARMIL2. Immunoblotting demonstrated the absence of CARMIL2 protein in all four patients and confirmed the diagnosis of CARMIL2 deficiency. T cells were activated in-vitro with addition of IL-2 in different concentrations. CD25 and interferon-gamma (IFNgamma) levels were measured after 48 h and 5 days of activation. CD25 surface expression on activated CD8(+) and CD4(+) T cells was significantly diminished in all patients compared to healthy controls. Additionally, CD8(+) T cells from all patients demonstrated significantly reduced IFNgamma production. When cells derived from CARMIL2-deficient patients were treated with IL-2, CD25 and IFNgamma production increased in a dose-dependent manner. T cell proliferation, as measured by Cell Trace-Violet, was impaired in one patient and it was also rescued with IL-2. In conclusion, we found that IL-2 rescued T cell activation and proliferation in CARMIL2-deficient patients. Thus, IL-2 should be further studied as a potential therapeutic modality for these patients.