Involvement of Rap-1 activation and early termination of immune synapse in CTLA-4-mediated negative signal

Satoru Hara, Chiaki Nakaseko, Sho Yamasaki, Masakazu Hattori, Johannes L. Bos, Yasushi Saito, Nagahiro Minato, Takashi Saito

    研究成果: ジャーナルへの寄稿記事

    10 引用 (Scopus)

    抜粋

    Netherlands Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T cell co-stimulation receptor that delivers inhibitory signals upon activation. This inhibitory effect by CTLA-4 requires activation of small GTPase Rap-1. However, the precise mechanism underlying these negative signals remains unclear. Here, we show that CTLA-4-induced suppression of IL-2 production correlates with rapid destabilization of immunological synapse (IS) formation in murine normal T cell clones. Overexpression of Spa-1, a Rap-1-specific GTPase activating protein (GAP), abolished both Rap-1 activation and IL-2 suppression induced by CTLA-4. Although we failed to find any specific inhibition of activation of early signals upon CTLA-4 engagement, we found that CTLA-4 specifically up-regulates cell motility and suppresses prolonged accumulation of Talin at the contact area with antigen presenting cells upon antigen stimulation. These results suggest that Rap-1 is activated upon CTLA-4 ligation and mediates inhibitory signals through prevention of IS formation.

    元の言語英語
    ページ(範囲)150-158
    ページ数9
    ジャーナルHematology
    14
    発行部数3
    DOI
    出版物ステータス出版済み - 6 1 2009

      フィンガープリント

    All Science Journal Classification (ASJC) codes

    • Hematology

    これを引用

    Hara, S., Nakaseko, C., Yamasaki, S., Hattori, M., Bos, J. L., Saito, Y., ... Saito, T. (2009). Involvement of Rap-1 activation and early termination of immune synapse in CTLA-4-mediated negative signal. Hematology, 14(3), 150-158. https://doi.org/10.1179/102453309X402241