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Published on: August 13, 2013
Phenotypic Analysis of CD4+ Treg, CD8+ Treg, and Breg Cells in Adult Common Variable Immunodeficiency Patients
Sait Yesillik1, Sudhanshu Agrawal1, Sastry V Gollapudi1
1Division of Basic and Clinical Immunology, University of California, Irvine, California, USA.
Insights
Regulatory lymphocytes, including CD4+ T regulatory cells (Treg) and CD8+ Treg, are reduced in patients with Common Variable Immunodeficiency (CVID). This finding suggests a role for these cells in CVID pathogenesis.
Area of Science:
- Immunology
- Cell Biology
Background:
- Regulatory lymphocytes, such as CD4+ T regulatory cells (Treg), CD8+ Treg, and B regulatory cells (Breg), are crucial for maintaining immune homeostasis and tolerance.
- Common Variable Immunodeficiency (CVID) is characterized by increased susceptibility to infections and a higher incidence of inflammatory and autoimmune conditions.
- While CD4+ Treg abnormalities are known in CVID, the status of CD8+ Treg cells remains largely uninvestigated.
Purpose of the Study:
- To investigate the proportions of CD4+ Treg and CD8+ Treg cells in patients diagnosed with CVID.
- To compare the levels of natural and induced regulatory T cells (Treg) and B regulatory cells (Breg) between CVID patients and healthy controls.
Main Methods:
- Flow cytometry was employed to analyze regulatory lymphocyte populations in 25 CVID patients and age-matched healthy controls.
- Peripheral blood mononuclear cells were analyzed for natural (nCD4+ Treg, nCD8+ Treg) and induced (iCD4+ Treg, iCD8+ Treg) Treg cells, as well as Breg cells, after in vitro activation.
Main Results:
- Significantly lower proportions of natural CD4+ Treg (nCD4+ Treg) and induced CD4+ Treg (iCD4+ Treg) were observed in CVID patients compared to controls.
- Patients with CVID also exhibited significantly reduced levels of induced CD8+ Treg (iCD8+ Treg) and B regulatory cells (Breg).
Conclusions:
- The study identified significant reductions in multiple regulatory lymphocyte subsets in CVID patients.
- These alterations in regulatory lymphocytes may contribute to the underlying pathogenesis of inflammation and autoimmunity observed in CVID.
Introduction:
Regulatory lymphocytes (CD4+ T regulatory cells [Treg], CD8+ Treg, and B regulatory cells [Breg]) play a critical role in immune homeostasis and tolerance. Common variable immunodeficiency (CVID) is associated with increased susceptibility to infections and increased frequency of inflammatory and autoimmune diseases. CD4+ Treg cell abnormalities have been reported in CVID; however, CD8+ Treg cells have not been reported in CVID. The objective of this study was to evaluate CD4+ Treg and CD8+ Treg cells in CVID patients.
Methods:
In 25 patients with CVID and age-matched healthy controls, Treg cells, evaluated in freshly isolated peripheral blood mononuclear cells (natural; nCD4+ Treg and nCD8+ Treg) and following in vitro activation with anti-CD3/CD28 monoclonal antibodies (induced; iCD4+ Treg and iCD8+ Treg) as well as Breg cells were analyzed with specific monoclonal antibodies and isotype controls using flow cytometry.
Results:
The proportions of nCD4+ Treg (CD4+ CD127low CD25high FoxP3+), iCD4+ Treg (CD4+ CD127low CD25high FoxP3+), iCD8+ Treg (CD8+ CD25high CD183+ FoxP3+), and Breg (CD19+ CD24high CD38high) lymphocytes were significantly lower in patients with CVID than in controls.
Conclusions:
Altered regulatory lymphocytes may play a role in the pathogenesis and autoimmunity and inflammation associated with CVID.
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