Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration

Makoto Kurachi, Junko Kurachi, Fumiko Suenaga, Tatsuya Tsukui, Jun Abe, Satoshi Ueha, Michio Tomura, Kei Sugihara, Shiki Takamura, Kazuhiro Kakimi, Kouji Matsushima

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Strength of inflammatory stimuli during the early expansion phase plays a crucial role in the effector versus memory cell fate decision of CD8+ T cells. But it is not known how early lymphocyte distribution after infection has an impact on this process. We demonstrate that the chemokine receptor CXCR3 is involved in promoting CD8+ T cell commitment to an effector fate rather than a memory fate by regulating T cell recruitment to an antigen/inflammation site. After systemic viral or bacterial infection, the contraction of CXCR3-/- antigen-specific CD8+ T cells is significantly attenuated, resulting in massive accumulation of fully functional memory CD8+ T cells. Early after infection, CXCR3-/- antigen-specific CD8+ T cells fail to cluster at the marginal zone in the spleen where inflammatory cytokines such as IL-12 and IFN-α are abundant, thus receiving relatively weak inflammatory stimuli. Consequently, CXCR3-/- CD8+ T cells exhibit transient expression of CD25 and preferentially differentiate into memory precursor effector cells as compared with wild-type CD8+ T cells. This series of events has important implications for development of vaccination strategies to generate increased numbers of antigen-specific memory CD8+ T cells via inhibition of CXCR3-mediated T cell migration to inflamed microenvironments.

Original languageEnglish
Pages (from-to)1605-1620
Number of pages16
JournalJournal of Experimental Medicine
Volume208
Issue number18
DOIs
Publication statusPublished - Aug 1 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Chemokine receptor CXCR3 facilitates CD8<sup>+</sup> T cell differentiation into short-lived effector cells leading to memory degeneration'. Together they form a unique fingerprint.

  • Cite this

    Kurachi, M., Kurachi, J., Suenaga, F., Tsukui, T., Abe, J., Ueha, S., Tomura, M., Sugihara, K., Takamura, S., Kakimi, K., & Matsushima, K. (2011). Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration. Journal of Experimental Medicine, 208(18), 1605-1620. https://doi.org/10.1084/jem.20102101