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Updated: Jun 18, 2026
Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Influence of membrane CD25 stability on T lymphocyte activity: implications for immunoregulation
Todd M Brusko1, Clive H Wasserfall, Maigan A Hulme
1Department of Pathology, University of Florida, Gainesville, Florida, United States of America.
Insights
Soluble CD25 (sCD25) indicates T cell activation and cell death. Its role in immune response depends on the inflammatory environment, affecting T cell proliferation and regulatory functions.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- CD25, an IL-2 receptor component, is crucial for T cell regulation and implicated in autoimmune disorders.
- Soluble CD25 (sCD25) is a potential biomarker for autoimmune susceptibility, but its functional impact is unclear.
Purpose of the Study:
- Investigate the functional impact of CD25 cleavage and sCD25 on immunoregulatory activities.
- Determine the role of sCD25 in T cell proliferation, activation, and cell death.
Main Methods:
- Examined sCD25 generation by regulatory T cells (Tregs) and effector T cells (Teffs) during in vitro suppression assays.
- Assessed the effect of sCD25 supplementation on Teff proliferation and Treg function under serum-free conditions.
Main Results:
- Teff cells increased CD25 expression and sCD25 release correlated with proliferation.
- Tregs lost suppressive function in serum-free conditions, which was partially restored by sCD25 supplementation.
- sCD25 production correlated with cell death in T cell cultures.
Conclusions:
- sCD25 serves as a marker for T cell activation and subsequent cell death.
- CD25's immunomodulatory role is context-dependent, influenced by the inflammatory milieu and molecules affecting its expression.
Background:
CD25, a component of the IL-2 receptor, is important in T cell proliferation, activation induced cell death, as well as the actions of both regulatory (Treg) and effector (Teff) T cells. Recent genome wide association studies have implicated the CD25 locus as an important region for genetic susceptibility to a number of autoimmune disorders, with serum levels of soluble CD25 receptor (sCD25) serving as a potential phenotypic marker for this association. However, the functional impact of CD25 cleavage, as well as the influence of sCD25 on immunoregulatory activities, remain largely unknown and form the basis of this effort.
Methodology/Principal Findings:
The generation of sCD25 by Treg (CD4(+)CD25(+)) and Teff (CD4(+)CD25(-)) cells was examined during in vitro suppression assays, efforts that demonstrated constitutive and stable surface CD25 expression on Treg throughout the period of in vitro assessment. In contrast, Teff cells increased CD25 expression during the process of in vitro suppression, with supernatant sCD25 levels correlating to the amount of cellular proliferation. Interestingly, under serum-free conditions, Tregs partially lost their characteristic anergic and suppressive properties. sCD25 supplementation at physiological concentrations to serum free in vitro suppression assays reduced Teff proliferation without specifically influencing suppression. Indeed, sCD25 production within these cultures correlated with cell death.
Conclusions/Significance:
These results support the notion that sCD25 functions as both a surrogate marker of T cell activation as well as an indicator of subsequent cellular death. In addition, the role of CD25 in immunomodulation is likely dependent on the local inflammatory milieu, with molecules capable of modulating surface CD25 expression playing a key role in defining immune responsiveness.
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