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Quantitative Imaging of Lineage-specific Toll-like Receptor-mediated Signaling in Monocytes and Dendritic Cells from Small Samples of Human Blood
Published on: April 16, 2012
IgE regulation and lymphokine patterns in aging humans.
H al-Rayes1, W Pachas, N Mirza
1Children's Hospital/Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
The Journal of Allergy and Clinical Immunology
|October 1, 1992
Summary
Aging impairs T-cell activation, leading to reduced interleukin-4 (IL-4) and immunoglobulin E (IgE) production. This age-related defect explains the decline in allergic responses observed in older adults.
Area of Science:
- Immunology
- Gerontology
- Cellular Biology
Background:
- Immunoglobulin E (IgE) production naturally decreases with age, correlating with improved allergic symptoms.
- Aging serves as a valuable in vivo model for investigating the regulation of IgE.
- Previous studies suggest age-related changes in immune responses, but the specific mechanisms affecting IgE production remain unclear.
Purpose of the Study:
- To investigate the mechanisms underlying age-related decline in IgE production.
- To compare IgE production and T-cell responses between young and older nonatopic individuals.
- To identify potential defects in T-cell signaling pathways associated with aging.
Main Methods:
- Compared IgE production in response to exogenous interleukin-4 (IL-4) in older (≥60 years) and young (15-30 years) nonatopic individuals.
- Assessed IL-4 and interferon-gamma (IFN-γ) production by mononuclear cells after stimulation with concanavalin A (surface receptor) and phorbol esters/ionophore (bypass signaling).
- Measured intracellular calcium (Ca+2) fluxes following CD3 crosslinking to evaluate T-cell membrane signal transduction.
Main Results:
- Exogenous IL-4 induced equivalent IgE production in both age groups, indicating preserved IL-4 responsiveness.
- Concanavalin A stimulation resulted in approximately 50% less IL-4 and a threefold reduction in IFN-γ production in older subjects compared to young subjects.
- Stimulation bypassing surface receptors yielded comparable IL-4 and IFN-γ levels in both age groups.
- Significantly decreased Ca+2 fluxes were observed in older individuals after CD3 crosslinking, confirming impaired T-cell signal transduction.
Conclusions:
- Aging is associated with an impairment in T-cell membrane signal transduction.
- This age-dependent T-cell activation defect leads to reduced IL-4 availability.
- The diminished IL-4 production contributes to the waning of IgE responses and allergic symptoms in older individuals.
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