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Spontaneous and glucocorticoid-induced apoptosis in human mature T lymphocytes
M Brunetti1, N Martelli, A Colasante
1Department of Human Pathology, G. D'Annunzio University, Chieti, Italy.
Abstract:
Glucocorticoid (GC)-induced apoptosis is a well-recognized physiologic regulator of murine T-cell number and function. We have analyzed its mechanisms in human mature T cells, which have been thought to be insensitive until recently. Peripheral blood T cells showed sensitivity to GC-induced apoptosis soon after the proliferative response to a mitogenic stimulation, and were also sensitive to spontaneous (ie, growth factor deprivation-dependent) apoptosis. CD8+ T cells were more sensitive to both forms than CD4+ T cells. Acquisition of sensitivity to GC-induced apoptosis was not associated with any change in number or affinity of GC receptors. Both spontaneous and GC-induced apoptosis were increased by the macromolecular synthesis inhibitors, cycloheximide (CHX) and puromycin. A positive correlation between the degree of protein synthesis inhibition and the extent of apoptosis was observed. Interleukin-2 (IL-2) IL-4, and IL-10 protected (IL-2 > IL-10 > IL-4) T cells from both forms of apoptosis in a dose-dependent manner. Our data suggest that spontaneous and GC-induced apoptosis regulate the human mature T-cell repertoire by acting early after the immune response and differentially affecting T-cell subsets.
Insights
Human mature T cells, previously thought insensitive, undergo glucocorticoid (GC)-induced apoptosis and spontaneous cell death. CD8+ T cells are more susceptible than CD4+ T cells, with interleukins modulating this process.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Glucocorticoids (GCs) regulate T-cell homeostasis in mice.
- Human mature T cells were historically considered resistant to GC-induced apoptosis.
- Recent findings suggest sensitivity in human T cells.
Purpose of the Study:
- Investigate the mechanisms of GC-induced apoptosis in human mature T cells.
- Determine the sensitivity of human T cells to spontaneous and GC-induced apoptosis.
- Analyze the role of T-cell subsets and cytokines in these apoptotic processes.
Main Methods:
- Analysis of peripheral blood T cells.
- Assessment of sensitivity to GC-induced and spontaneous apoptosis.
- Use of macromolecular synthesis inhibitors (cycloheximide, puromycin).
- Evaluation of cytokine protection (IL-2, IL-4, IL-10).
Main Results:
- Human mature T cells exhibit sensitivity to GC-induced apoptosis post-mitogenic stimulation.
- CD8+ T cells are more sensitive than CD4+ T cells to both apoptotic forms.
- Protein synthesis inhibition correlates positively with apoptosis extent.
- Interleukins (IL-2, IL-10, IL-4) provide dose-dependent protection against apoptosis.
Conclusions:
- Spontaneous and GC-induced apoptosis are active regulators of the human mature T-cell repertoire.
- These processes occur early after immune responses.
- Apoptosis differentially affects CD4+ and CD8+ T-cell subsets.