%0 Journal Article
%T Increased Cholesterol Content in Gammadelta (¦Ã¦Ä) T Lymphocytes Differentially Regulates Their Activation
%A Hsin-Yuan Cheng
%A Runpei Wu
%A Abraham K. Gebre
%A Richard N. Hanna
%A Dan J. Smith
%A John S. Parks
%A Klaus Ley
%A Catherine C. Hedrick
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0063746
%X Gammadelta (¦Ã¦Ä) T lymphocytes respond quickly upon antigen encounter to produce a cytokine response. In this study, we sought to understand how functions of ¦Ã¦Ä T cells are differentially regulated compared to ¦Á¦Â T cells. We found that cholesterol, an integral component of the plasma membrane and a regulator of TCR signaling, is increased in ¦Ã¦Ä T cells compared to ¦Á¦Â T cells, and modulates their function. Higher levels of activation markers, and increased lipid raft content in ¦Ã¦Ä cells suggest that ¦Ã¦Ä T cells are more activated. Cholesterol depletion effectively decreased lipid raft formation and activation of ¦Ã¦Ä T cells, indicating that increased cholesterol content contributes to the hyper-activated phenotype of ¦Ã¦Ä 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 ¦Ã¦Ä T cells. Our data indicate that cholesterol metabolism is differentially regulated in ¦Ã¦Ä T cells. The high intracellular cholesterol content leads to enhanced TCR signaling and increases activation and proliferation of ¦Ã¦Ä T cells.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063746