Critical role of lipid rafts in CD154-mediated T cell signaling

Eur J Immunol. 2010 Mar;40(3):770-9. doi: 10.1002/eji.200939646.

Abstract

Although signal pathways triggered via the CD40 molecule are well characterized, those induced via CD154 are less known. This study demonstrates that engagement of CD154 in Jurkat D1.1 cells with soluble CD40 leads to PKC alpha and delta activation, calcium mobilization, and phosphorylation of the Map kinases ERK1/2 and p38. Such response is accompanied by significant recruitment of CD154 into lipid rafts. Disruption of lipid rafts integrity with nystatin or methyl beta-cyclodextrin abrogated PKCalpha PKCdelta and p38 phosphorylation, but had no effect on ERK1/2 phosphorylation. Inhibition of PKC activation completely abolished p38 phosphorylation but had no effect on ERK1/2 phosphorylation, suggesting that localization of CD154 within lipid rafts is an absolute requirement for CD154-induced PKCalpha- and PKCdelta-dependent p38 phosphorylation. Furthermore, CD154 acts as co-stimulator for the production of IL-2 in an APC-superantigen-T-cell activation model. The results obtained demonstrate for the first time, that lipid rafts are of immunological relevance for CD154-triggered signals, and reinforce the importance of CD154 in T-cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • CD40 Ligand / immunology*
  • CD40 Ligand / metabolism
  • Cell Separation
  • Flow Cytometry
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / immunology*
  • Membrane Microdomains / immunology*
  • Membrane Microdomains / metabolism
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • CD40 Ligand