Tyk2-dependent bystander activation of conventional and nonconventional Th1 cell subsets contributes to innate host defense against listeria monocytogenes infection

Tomomitsu Hashiguchi, Akiko Oyamada, Koji Sakuraba, Kazuya Shimoda, Keiichi I. Nakayama, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

IL-12, which is produced in response to intracellular bacteria, such as Listeria monocytogenes, promotes the development of pathogen-specific Th1 cells that play an important role in host defense. However, it has also been known that CD44high memoryphenotype CD4 T cells with Th1 functions naturally occur in naive mice, and that lymphopenia-induced proliferation of naive CD4 T cells generates memory-phenotype CD4 T cells with Th1 functions, although their differentiation mechanism and contribution to host defense are unclear. In this study, we analyzed the development and the functions of the different subsets of Th1 cells by using mice lacking tyrosine kinase 2 (Tyk2), a member of the Janus kinase family critically involved in IL-12 signaling. In contrast with the case of conventional Ag-specific Th1 cells, the development of naturally occurring Th1 cells was not impaired in Tyk2-deficient mice. In addition, Th1 cells were normally generated from Tyk2-deficient naive CD4 T cells via lymphopeniainduced proliferation. Nevertheless, all these Th1 subsets, including conventional Ag-induced Th1 cells, produced IFN-g in response to IL-12 in a Tyk2-dependent manner. Importantly, such Tyk2-dependent bystander IFN-g production of any Th1 subsets conferred early protection against L. monocytogenes infection. Thus, Tyk2-mediated IL-12 signaling is differentially required for the development of different Th1 cell subsets but similarly induces their bystander IFN-g production, which contributes to innate host defense against infection with intracellular bacteria.

Original languageEnglish
Pages (from-to)4739-4747
Number of pages9
JournalJournal of Immunology
Volume192
Issue number10
DOIs
Publication statusPublished - May 15 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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