Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo

Chiaki Iwamura, Kenta Shinoda, Yusuke Endo, Yukiko Watanabe, Damon John Tumes, Shinichiro Motohashi, Kazuyoshi Kawahara, Yuki Kinjo, Toshinori Nakayama

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms of immunological memory. Factors regulating memory CD4+ T helper (Th)-cell pool size and function remain unclear, however. We show that activation of type I invariant natural killer T (iNKT) cells with glycolipid ligands and activation of type II natural killer T (NKT) cells with the endogenous ligand sulfatide induced dramatic proliferation and expansion of memory, but not naïve, CD4 T cells. NKT cell-induced proliferation of memory Th1 and Th2 cells was dependent largely on the production of IL-2, with Th2-cell proliferation also affected by loss of IL-4. Type II NKT cells were also required for efficient maintenance of memory CD4 T cells in vivo. Activation of iNKT cells resulted in up-regulation of IFN-γ expression by memory Th2 cells. These IFN-γ-producing memory Th2 cells showed a decreased capability to induce Th2 cytokines and eosinophilic airway inflammation. Thus, activated NKT cells directly regulate memory CD4 T-cell pool size and function via the production of cytokines in vivo.

Original languageEnglish
Pages (from-to)16992-16997
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number42
DOIs
Publication statusPublished - 16 Oct 2012

Keywords

  • Allergy
  • CD1d KO mice
  • Jα18 KO mice
  • STAT5
  • α-galactosylceramide

ASJC Scopus subject areas

  • General

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