A critical role for IL-12 in CCR5 induction on T cell receptor-triggered mouse CD4+ and CD8+ T cells

Masayuki Iwasaki, Takao Mukai, Ping Gao, Woong Ryeon Park, Chigusa Nakajima, Michio Tomura, Hiromi Fujiwara, Toshiyuki Hamaoka

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Despite increasing evidence for the role of the chemokine system in leukocyte trafficking, the mechanism underlying the induction of chemokine receptors is poorly understood. Here, we investigated how CCR5, a chemokine receptor implicated in T cell migration to inflammatory sites, is induced in the T cell. CCR5 mRNA was hardly detected in resting T cells and marginally induced following T cell receptor (TCR) stimulation. However, TCR-triggered T cells expressed IL-12 receptor, and stimulation with recombinant IL-12 resulted in high levels of CCR5 expression on both CD4+ and CD8+ T cells. In contrast, IL-2 failed to up-regulate CCR5 expression. The effect of IL-12 was selective to CCR5 because IL-12 did not up-regulate CXCR3 expression. Surface expression of CCR5 was shown by staining with anti-CCR5 monoclonal antibody. Stimulation of these CCR5-positive T cells with the relevant chemokine MIP-1α elicited Ca2+ influx, showing that IL-12-induced CCR5 is functional. These results indicate a critical role for IL-12 in the induction of CCR5 on TCR-triggered T cells.

Original languageEnglish (US)
Pages (from-to)2411-2420
Number of pages10
JournalEuropean Journal of Immunology
Volume31
Issue number8
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • CCR5
  • Chemokine
  • Chemokine receptor
  • IL-12
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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