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Stress modulates calcium mobilization in immune cells
Y Sei1, T McIntyre, P Skolnick
1Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Insights
Restraint stress impacts immune cell calcium signaling. Acute stress alters T-cell responses, while chronic stress temporarily suppresses calcium increases in CD4+ T cells and B cells, potentially leading to immunosuppression.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Stress significantly impacts immune function.
- Calcium signaling is crucial for lymphocyte activation.
- Understanding stress-induced immune modulation is vital for health.
Purpose of the Study:
- To investigate the effects of acute and chronic restraint stress on mitogen-induced calcium signaling in mouse spleen lymphocytes.
- To analyze stress-induced changes in specific lymphocyte subpopulations (CD4+ T cells, CD8+ T cells, B cells).
Main Methods:
- Dual-color flow cytometry was used to analyze cytoplasmic free-calcium concentrations ([Ca2+]i) in lymphocyte subpopulations.
- Mice were subjected to acute (2-hour) or chronic (2 hours daily for up to 21 days) restraint stress.
- Mitogen stimulation was employed to assess calcium responses.
Main Results:
- Acute stress suppressed [Ca2+]i in CD4+ T cells but enhanced it in CD8+ T cells.
- Chronic stress (3 and 7 days) suppressed [Ca2+]i in CD4+ T cells, with effects diminishing by day 21.
- Chronic stress had a modest suppressive effect on B cell calcium responses; CD8+ T cells were unaffected.
- Stress predominantly affected CD4+ T cells, potentially reversing CD4/CD8 ratios and impacting immune responses.
Conclusions:
- Stress significantly modulates calcium mobilization in lymphocytes.
- Altered calcium signaling in lymphocytes, particularly CD4+ T cells, may be an early mechanism of stress-induced immunosuppression.
- These findings highlight the intricate link between stress, calcium signaling, and immune function.
Abstract:
Both acute and chronic restraint stress modulated mitogen-induced increases in cytoplasmic free-calcium concentrations ([Ca2+]i) in mouse spleen cells. Dual-color analysis of lymphocyte subpopulations demonstrated that acute (2 hour) restraint stress suppressed mitogen-stimulated increases in [Ca2+]i in CD4+ T cells, but enhanced [Ca2+]i in CD8+ T cells. Chronic restraint stress (2 hours daily for up to 21 days) resulted in a significant suppression of mitogen-stimulated increases in [Ca2+]i in CD4+ T cells at 3 and 7 days, but not at 21 days. CD8+ T cells were unaffected by chronic stress. Chronic stress (for 7 days) had a modest suppressive effect on mitogen-induced Ca2+ responses in B cells. Within T lymphocyte subpopulations, both acute and chronic stress predominantly affected CD4+ T cells, which may induce a functional reversal of the CD4/CD8 ratios in vivo. Such a reversal could result in suppression of a variety of immune responses such as lymphocyte proliferation and antigen-specific antibody production. These findings indicate that the inhibitory effects of stress on calcium mobilization in lymphocytes may be an early event mediating stress-induced immunosuppression.
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