CRTAM confers late-stage activation of CD8+ T cells to regulate retention within lymph node

Arata Takeuchi, Yasushi Itoh, Akiko Takumi, Chitose Ishihara, Noriko Arase, Tadashi Yokosuka, Haruhiko Koseki, Shou Yamasaki, Yoshimi Takai, Jun Miyoshi, Kazumasa Ogasawara, Takashi Saito

    Research output: Contribution to journalArticle

    32 Citations (Scopus)

    Abstract

    In vivo immune response is triggered in the lymph node, where lymphocytes for entry into, retention at, and migration to effector sites are dynamically regulated. The molecular mechanism underlying retention regulation is the key to elucidating in vivo regulation of immune response. In this study, we describe the function of the adhesion molecule class I-restricted T cell-associated molecule (CRTAM) in regulating CD8+ T cell retention within the lymph node and eventually effector function. We previously identified CRTAM as a receptor predominantly expressed on activated CD8+ T cells, and nectin-like molecule-2 (Necl2) as its ligand. In vivo function of CRTAM-Necl2 interaction was analyzed by generating CRTAM-/- mice. CRTAM -/- mice exhibited reduced protective immunity against viral infection and impaired autoimmune diabetes induction in vivo. Although Agspecific CRTAM-/- CD8+ T cells showed normal CTL functions in vitro, their number in the draining lymph node was reduced. Because CRTAM+ T cells bound efficiently to Necl2-expressing CD8+ dendritic cells (DCs) that reside in T cell area of lymph node, CRTAM may induce retention by binding to CD8+ DCs at the late stage of activation before proliferation. The CRTAM-mediated late interaction with DCs induced retention of activated CD8+ T cells in an Ag-independent fashion, and this possibly resulted in effective CTL development in the draining lymph node.

    Original languageEnglish
    Pages (from-to)4220-4228
    Number of pages9
    JournalJournal of Immunology
    Volume183
    Issue number7
    DOIs
    Publication statusPublished - Oct 1 2009

    All Science Journal Classification (ASJC) codes

    • Immunology

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  • Cite this

    Takeuchi, A., Itoh, Y., Takumi, A., Ishihara, C., Arase, N., Yokosuka, T., Koseki, H., Yamasaki, S., Takai, Y., Miyoshi, J., Ogasawara, K., & Saito, T. (2009). CRTAM confers late-stage activation of CD8+ T cells to regulate retention within lymph node. Journal of Immunology, 183(7), 4220-4228. https://doi.org/10.4049/jimmunol.0901248