CD30 is required for activation of a unique subset of interleukin- 17A-Producing γδT Cells in innate immunity against mycobacterium bovis bacillus calmette-guérin infection

Ying Guo, Xun Sun, Kensuke Shibata, Hisakata Yamada, Hiromi Muta, Eckhard R. Podack, Yasunobu Yoshikai

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Interleukin-17A (IL-17A)-producing γδ T cells are known to be activated following Mycobacterium bovis bacillus Calmette- Guérin (BCG) infection. Here, we show that CD30, a member of the tumor necrosis factor (TNF) receptor superfamily, is important for activation of IL-17A-producing γδ T cells after BCG infection. Vγ1- Vγ4- γδ T cells preferentially expressing Vγ6/Vδ1 genes were identified as the major source of IL-17A in the peritoneal cavity during the early stage of BCG infection. The number of IL-17A-producing Vγ1- Vγ4- γδ T cells bearing Vγ6 increased in peritoneal exudate cells (PEC) of wild-type (WT) mice but not in those of CD30 knockout (KO) mice in response to BCG infection. Consistently, CD30 ligand (CD30L) or CD30 expression, predominantly by Vγ1- Vγ4- γδ T cells, was rapidly upregulated after BCG infection. Inhibition of CD30L/CD30 signaling by in vivo administration of a soluble CD30 and immunoglobulin fusion protein (CD30-Ig) severely impaired activation of IL-17Aproducing Vγ1- Vγ4- γδ T cells in WT mice, while stimulating CD30L/CD30 signaling by in vivo administration of agonistic anti-CD30 monoclonal antibody (MAb) restored IL-17A production by Vγ1- Vγ4- γδ T cells in CD30L KO mice after BCG infection. These results suggest that CD30 signaling plays an important role in the activation of IL-17A-producing Vγ1- Vγ4- γδ T cells bearing Vγ6 at an early stage of BCG infection.

Original languageEnglish
Pages (from-to)3923-3934
Number of pages12
JournalInfection and Immunity
Volume81
Issue number10
DOIs
Publication statusPublished - Sep 25 2013

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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