期刊
PLOS ONE
卷 8, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0063746
关键词
-
资金
- National Institutes of Health [P01HL055798, R01HL097368, R01HL049373, R01HL094525]
- American Diabetes Association Mentor-Based Postdoctoral Fellowship [7-12-MN-31]
Gammadelta (gamma delta) T lymphocytes respond quickly upon antigen encounter to produce a cytokine response. In this study, we sought to understand how functions of gamma delta T cells are differentially regulated compared to alpha beta T cells. We found that cholesterol, an integral component of the plasma membrane and a regulator of TCR signaling, is increased in gamma delta T cells compared to alpha beta T cells, and modulates their function. Higher levels of activation markers, and increased lipid raft content in gamma delta cells suggest that gamma delta T cells are more activated. Cholesterol depletion effectively decreased lipid raft formation and activation of gamma T cells, indicating that increased cholesterol content contributes to the hyper-activated phenotype of gamma delta T cells, possibly through enhanced clustering of TCR signals in lipid rafts. TCR stimulation assays and western blotting revealed that instead of a lower TCR threshold, enhanced TCR signaling through ERK1/2 activation is likely the cause for high cholesterol-induced rapid activation and proliferation in gamma delta T cells. Our data indicate that cholesterol metabolism is differentially regulated in gamma delta T cells. The high intracellular cholesterol content leads to enhanced TCR signaling and increases activation and proliferation of gamma delta T cells.
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