Shedded neuronal ICAM-5 suppresses T-cell activation

Li Tian, Jani Lappalainen, Matti Autero, Satu Hänninen, Heikki Rauvala, Carl G Gahmberg

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Intercellular adhesion molecules (ICAMs) bind to leukocyte beta 2 integrins, which, among other functions, provide costimulatory signals for T-cell activation. ICAM-5 (telencephalin) is expressed in the soma-dendritic region of neurons of the mammalian brain. The receptor for ICAM-5 is the integrin LFA-1, a major leukocyte integrin expressed in lymphocytes and microglia. In conditions of brain ischemia, epilepsy, and encephalitis, the soluble form of ICAM-5 (siCAM-5) has been detected in physiologic fluids. Here, we report that sICAM-5 attenuates the T-cell receptor-mediated activation of T cells as demonstrated by the decreased expression of the activation markers CD69, CD40L, and CD25 (IL-2R). This effect is most clearly seen in CD45RO(LOW) (naive), and not in CD45RO(High) (memory) T cells, and is most effective early in priming, but not in the presence of strong costimula- tory signals. Furthermore, sICAM-5 promotes the mRNA expression of the cytokines TGF-beta 1 and IFN-gamma, but not TNF. The formation of sICAM-5 is promoted by activated T cells through the cleavage of ICAM-5 from neurons. This suggests that ICAM-5 is involved in immune privilege of the brain and acts as an anti-inflammatory agent.
    Original languageEnglish
    JournalBlood
    Volume111
    Issue number7
    Pages (from-to)3615-3625
    Number of pages11
    ISSN0006-4971
    DOIs
    Publication statusPublished - 2008
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine
    • 118 Biological sciences
    • 515 Psychology

    Cite this

    Tian, L., Lappalainen, J., Autero, M., Hänninen, S., Rauvala, H., & Gahmberg, C. G. (2008). Shedded neuronal ICAM-5 suppresses T-cell activation. Blood, 111(7), 3615-3625. https://doi.org/10.1182/blood-2007-09-111179