Cellular cholesterol enrichment impairs T cell activation and chemotaxis

Dzung H. Nguyen, Juan C. Espinoza, Dennis D. Taub

Research output: Contribution to journalArticlepeer-review


Human aging is associated with an increase in immune cell cholesterol levels, independent of circulating cholesterol levels. The effects of such an increase in membrane cholesterol on lipid raft-associated immune cell function have not been investigated. We sought to examine the effects of in vitro cholesterol loading on two known lipid raft-associated pathways of T cells, namely T cell activation and chemokine stimulation. Using β-cyclodextrin (BCD) as a vehicle, we were able to rapidly load cholesterol onto human T cell lines and primary peripheral blood T cells without inducing significant cell toxicity. Loading of cholesterol to four-fold that of normal levels induced significant inhibition of intracellular calcium mobilization by both αCD3 and SDF-1α. Cholesterol-loaded peripheral T cells were completely unresponsive to αCD3/αCD28 stimulation, demonstrating no increase in IL-2, GM1 expression or cell size. T cell polarization of lipid rafts to αCD3/αCD28 beads was also impaired. In addition, cholesterol loading potently inhibited SDF-1α-induced chemotaxis. We propose that excess membrane cholesterol could potentially disrupt raft-related cell functions downstream of receptor triggering and that the loss of cholesterol regulation of aging immune cells could contribute to immune cell senescence.

Original languageEnglish (US)
Pages (from-to)641-650
Number of pages10
JournalMechanisms of Ageing and Development
Issue number9
StatePublished - Sep 2004


  • Chemotaxis
  • Cholesterol enrichment
  • T cell activation

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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