Invariant natural killer T cells are not affected by lysosomal storage in patients with Niemann-Pick disease type C

Research output: Contribution to journalArticlepeer-review

Authors

  • Anneliese O Speak
  • Nicholas Platt
  • Mariolina Salio
  • Danielle te Vruchte
  • David A Smith
  • Dawn Shepherd
  • Nicole M Yanjanin
  • Louise Simmons
  • Jackie Imrie
  • James E Wraith
  • Robin H Lachmann
  • Ralf Hartung
  • Heiko Runz
  • Eugen Mengel
  • Michael Beck
  • Christian J Hendriksz
  • Forbes D Porter
  • Vincenzo Cerundolo
  • Frances M Platt

Colleges, School and Institutes

Abstract

Invariant natural killer T (iNKT) cells are a specialised subset of T cells that are restricted to the MHC class I like molecule, CD1d. The ligands for iNKT cells are lipids, with the canonical superagonist being α-galactosylceramide, a non-mammalian glycosphingolipid. Trafficking of CD1d through the lysosome is required for the development of murine iNKT cells. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by dysfunction in either of two lysosomal proteins, NPC1 or NPC2, resulting in the storage of multiple lipids, including glycosphingolipids. In the NPC1 mouse model, iNKT cells are virtually undetectable, which is likely due to the inability of CD1d to be loaded with the selecting ligand due to defective lysosomal function and/or CD1d trafficking. However, in this study we have found that in NPC1 patients iNKT cells are present at normal frequencies, with no phenotypic or functional differences. In addi-tion, antigen-presenting cells derived from NPC1 patients are functionally competent to present several different CD1d/iNKT-cell ligands. This further supports the hypothesis that there are different trafficking requirements for the development of murine and human iNKT cells, and a functional lysosomal/late-endosomal compartment is not required for human iNKT-cell development.

Bibliographic note

© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Details

Original languageEnglish
Pages (from-to)1886-92
Number of pages7
JournalEuropean Journal of Immunology
Volume42
Issue number7
Publication statusPublished - 2012