Exogenous interleukin‐2 can rescue in‐vitro T cell activation and proliferation in patients with a novel capping protein regulator and myosin 1 linker 2 mutation
Summary 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 prolifera...
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Veröffentlicht in: | Clinical and experimental immunology 2020-06, Vol.200 (3), p.215-227 |
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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; aged 2·5–10 years at presentation). The patients presented with inflammatory bowel disease and recurrent viral infections. Genetic analysis revealed a novel homozygous 25‐base pairs 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 the addition of IL‐2 in different concentrations. CD25 and interferon (IFN)‐γ 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 IFN‐γ production. When cells derived from CARMIL2‐deficient patients were treated with IL‐2, CD25 and IFN‐γ 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.
CARMIL2 deficiency is characterized by impaired T cell activation and proliferation, recurrent infections and reduced regulatory T cell counts. Interleukin (IL‐2) can rescue in‐vitro T cell activation and proliferation of CARMIL2‐deficient patients. IL‐2 should be further studied as a potential therapeutic modality in CARMIL2‐deficient patients. |
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ISSN: | 0009-9104 1365-2249 1365-2249 |
DOI: | 10.1111/cei.13432 |