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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.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2020 Jun; Vol. 200 (3), pp. 215-227. Date of Electronic Publication: 2020 Apr 18. - Publication Year :
- 2020
-
Abstract
- 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 <superscript>+</superscript> and CD4 <superscript>+</superscript> T cells was significantly diminished in all patients compared to healthy controls. Additionally, CD8 <superscript>+</superscript> 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.<br /> (© 2020 British Society for Immunology.)
- Subjects :
- CD8-Positive T-Lymphocytes pathology
Child
Child, Preschool
Female
Humans
Inflammatory Bowel Diseases genetics
Inflammatory Bowel Diseases immunology
Inflammatory Bowel Diseases pathology
Lymphocyte Activation genetics
Male
Virus Diseases genetics
Virus Diseases immunology
Virus Diseases pathology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Cell Proliferation drug effects
Interleukin-2 pharmacology
Lymphocyte Activation drug effects
Microfilament Proteins deficiency
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2249
- Volume :
- 200
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32201938
- Full Text :
- https://doi.org/10.1111/cei.13432