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Published on: January 15, 2011
Prothymosin alpha enhances interleukin 2 receptor expression in normal human T-lymphocytes
O J Cordero1, C S Sarandeses, J L López
1Departamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad de Santiago, Spain.
Insights
Prothymosin alpha (Pro alpha) enhances human peripheral blood mononuclear cell (PBMC) proliferation by increasing interleukin-2 receptor (IL-2R) expression, particularly in cells with suboptimal responses. This suggests potential therapeutic applications for immunodeficiency and aging.
Area of Science:
- Immunology
- Cell Biology
Background:
- Prothymosin alpha (Pro alpha) is known to modulate immune responses.
- Phytohaemagglutinin (PHA) stimulates human peripheral blood mononuclear cells (PBMC) proliferation.
- Interleukin-2 receptor (IL-2R) is crucial for T-cell activation and proliferation.
Purpose of the Study:
- To investigate if Pro alpha enhances PBMC proliferation by affecting IL-2R expression.
- To determine if Pro alpha influences the number of IL-2R-expressing cells or IL-2R surface density.
- To explore the role of macrophages and IL-2 in Pro alpha's immunomodulatory effects.
Main Methods:
- PBMC from 21 donors were stimulated with PHA at optimal and diluted concentrations.
- Pro alpha's effect on IL-2R expression (cell number and density) and proliferation was assessed.
- Cyclosporin A was used to suppress IL-2 production to evaluate its role.
Main Results:
- Pro alpha significantly increased IL-2R expression in cells with half-maximal responses to PHA (groups Lh and Hl).
- Pro alpha-mediated enhancement of IL-2R expression in group Lh was dose-dependent and correlated with increased proliferation.
- Pro alpha's effect was independent of IL-2 and required macrophages for modulation of PHA-stimulated IL-2R expression.
Conclusions:
- Pro alpha enhances PBMC proliferation by upregulating IL-2R expression, particularly in suboptimal conditions.
- The mechanism appears independent of IL-2 but requires macrophage involvement during lymphocyte activation.
- Pro alpha holds potential for treating T-cell dysfunction in immunodeficiency and aging populations.
Abstract:
We investigated whether the enhancement, by prothymosin alpha (Pro alpha), of the phytohaemagglutinin-stimulated proliferation of human peripheral blood mononuclear cells (PBMC) is due to its affect on the number of cells expressing the interleukin 2 receptor (IL-2R) or the surface density of IL-2R on PBMC. Peripheral blood mononuclear cells were obtained from 21 donors. For both an optimal phytohaemagglutinin (PHA) concentration (H) and a 10-fold dilution (L), their responses fell in two classes, high (h) and low (l), making four dose--response situations. Pro alpha significantly increased the number and IL-2R density of cells expressing IL-2R only when the response in its absence was about half maximal, i.e. for PBMC responding well to the low PHA stimulus (group Lh) or PBMC responding poorly to the optimal stimulus (group Hl). The enhancement of IL-2R expression in group Lh by Pro alpha was dose-dependent and paralleled by increased proliferative response. It appears not to be mediated by IL-2, since it was unaffected when IL-2 production was suppressed by cyclosporin A. The early interaction of Pro alpha with lymphocytes did not require the presence of macrophages, but macrophages were necessary during lymphocyte activation for modulation of PHA-stimulated IL-2R expression to be affected. The immunoregulatory activity of Pro alpha may prove useful for improving the decreased T-cell function associated with immunodeficiency, or for restoration of normal IL-2R expression by the lymphocytes of aged individuals.
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