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T-cell activation and the development of an apoptosis-resistant CD45RO+ T-cell population
M Müller1, J Grunewald, D Gigliotti
1Department of Medicine, Division of Respiratory Medicine, Karolinska Institutet, Stockholm, Sweden. malin.muller@ks.se
Abstract:
Growing experimental evidence supports a broadening role for the caspases; not only do they participate in the process of apoptosis but also in the control of the cell cycle and cellular proliferation. The biological role of the caspases in the process of T-cell activation and proliferation is still not defined. In the present study, we propose a potential role, by demonstrating an association of T-cell receptor-mediated caspase activity with the development of an apoptosis-resistant memory CD45RO+ T-cell population. As previously shown by us, a time-dependent induction of caspase activity, in the absence of apoptosis, can be observed in CD3-stimulated human peripheral blood lymphocytes. We here show that a population of CD45RO+ cells, with activated caspase-3 and with resistance to tributyltin-induced apoptosis, develops after 3 days of stimulation. A concomitant expression of the anti-apoptotic protein Bcl-xL accompanied the caspase activity and the development of the apoptosis-resistant phenotype. Finally, upon co-culturing with dexamethasone (DEX), the CD3-induced caspase-3 activity was blocked. During this condition, the expression of the activation marker HLA-DR as well as the cellular proliferative response was strongly suppressed. The development of memory cells with a CD45RO+ phenotype was also blocked. Our data support the hypothesis that caspase-3 activity, observed in CD3-stimulated cells, may be an important component in the proliferation process and, furthermore, might play a role for the development of memory T cells, and DEX inhibits this process.
Insights
Caspase-3 activity in T-cells promotes proliferation and memory cell development. Dexamethasone blocks this caspase activity, suppressing T-cell activation and memory cell formation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Caspases are known for their role in apoptosis.
- Their function in T-cell activation, proliferation, and memory cell development is not fully understood.
- Previous studies showed caspase activity induction in CD3-stimulated lymphocytes without apoptosis.
Purpose of the Study:
- To investigate the role of caspases in T-cell activation and proliferation.
- To determine the association between T-cell receptor-mediated caspase activity and apoptosis-resistant memory T-cell populations.
- To explore the effect of dexamethasone on T-cell caspase activity and proliferation.
Main Methods:
- Stimulation of human peripheral blood lymphocytes with CD3.
- Analysis of caspase activity, apoptosis resistance, and Bcl-xL expression.
- Co-culturing with dexamethasone (DEX) to assess its inhibitory effects.
- Monitoring of HLA-DR expression and cellular proliferation.
Main Results:
- A CD45RO+ T-cell population with activated caspase-3 and resistance to apoptosis developed after 3 days of CD3 stimulation.
- Concomitant expression of Bcl-xL was observed with caspase activity and apoptosis resistance.
- Dexamethasone blocked CD3-induced caspase-3 activity, suppressed HLA-DR expression, proliferation, and memory cell development.
Conclusions:
- Caspase-3 activity in CD3-stimulated T-cells is crucial for proliferation and memory T-cell development.
- Dexamethasone inhibits T-cell proliferation and memory cell development by blocking caspase-3 activity.
- These findings highlight a novel role for caspases in T-cell memory formation.