Shedded neuronal ICAM-5 suppresses T-cell activation.
Intercellular adhesion molecules (ICAMs) bind to leukocyte beta2 integrins, which, among other functions, provide costimulatory signals for T-cell activation. ICAM-5 (telencephalin) is expressed in the somadendritic region of neurons of the mammalian brain. The receptor for ICAM-5 is the integrin LFA-1, a major leukocyte integ-rin 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 CD45ROLow (naive), and not in CD45ROHigh (memory) T cells, and is most effective early in priming, but not in the presence of strong costimulatory signals. Furthermore, sICAM-5 promotes the mRNA expression of the cytokines TGF-beta1 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.
Tian
Li
L
Department of Biologic and Environmental Sciences, Faculty of Biosciences, University of Helsinki, Finland. li.tian@helsinki.fi
Lappalainen
Jani
J
Autero
Matti
M
Hänninen
Satu
S
Rauvala
Heikki
H
Gahmberg
Carl G
CG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001927:Brain Diseases / Q000276:immunology / Q000473:pathology; D018821:CD18 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003712:Dendrites / Q000276:immunology*; D006624:Hippocampus / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D017628:Microglia / Q000166:cytology / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D012333:RNA, Messenger / Q000276:immunology; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000954:Antigens, Surface; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; C086747:ICAM5 protein, human; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell