S12 Abstracts

skin graft itself or via the presentation of captured donor MHCmolecules (cross-dressing) by recipient APCs in the draininglymph nodes.

doi:10.1016/j.clim.2009.03.027

OR.21. MCAM/CD146 is Expressed by BrainEndothelial Cells and Defines a Unique EffectorMemory Lymphocyte Subset Involvedin NeuroinflammationRomain Cayrol1, Hania Kebir1, Igal Ifergan1, AuroreDodelet-Devillers1, Simone Terouz1, Arsalan Haqqani 2,Josee Poirier 3, Danica Stanimirovic 2, Pierre Duquette3,Nathalie Arbour1, Alexandre Prat3. 1Université de Montréal,Montréal, QC, Canada; 2National Research Council ofCanada, Ottawa, ON, Canada; 3Centre Hospitalier del'Université de Montréal, Montréal, QC, Canada

Immune cell infiltration to the central nervous system(CNS) is a hallmark of the disease Multiple Sclerosis (MS). InMS, BBB dysfunction is associated with increased expressionof adhesion molecules and chemokines leading to increasedleukocyte trafficking to the CNS. The reciprocal attachmentof leukocytes to BBB endothelial cells (BBB-ECs) is a key stepof this CNS infiltration. Cell adhesion molecules (CAM) of theof the immunoglobulin family (ICAM-1 and VCAM) are keyplayers in the interactions between the immune cells andthe BBB-ECs. To describe novel CAMs of the BBB we used alipid raft-based proteomic approach to identify an immu-noglobulin subfamily of proteins expressed by BBB-ECs.Melanoma cell adhesion molecule (MCAM/CD146) wasidentified in this screen and this project aims to character-ize MCAM's function in immune cell migration across theBBB. Our data demonstrates that MCAM is expressed on thesurface of BBB-ECs, in vitro and in situ and co-localizes withlymphocyte surface markers during adhesion and diapedesis.Since MCAM's only known ligand is MCAM itself, we analysedMCAM expression on peripheral blood leukocytes fromhuman healthy donors and MS patients. MCAM was detectedon a unique subset of effector memory CD4+and CD8+Tlymphocytes. In vitro polyclonal activation induced MCAMup-regulation on T lymphocytes. Moreover, we found thatMCAM+T lymphocytes produce significantly more inflamma-tory cytokines interferon-gamma and IL-17 compared toMCAMneg cells. Finally, the proportion of MCAM+T cells wasfound to be consistently higher in MS patients duringrelapses compared to non-relapsing patients and controls.Our data indicates that MCAM is expressed by both the BBBand peripheral blood immune cells and suggests that MCAMcould play an important role in CNS inflammatory reactions,including MS.

doi:10.1016/j.clim.2009.03.028

OR.22. Aβ-specific T Cell Trafficking to the Brainin a Mouse Model of ADYair Fisher, Rona Baron, Anna Nemirovsky, Alon Monsonego.Ben-Gurion University on the Negev, Be'er Sheva, Israel

Recent vaccination approaches showed remarkable effi-cacy of removal of amyloid β (Aβ) from the brains of micewith Alzheimer's-like disease, although vaccination of peoplehad to be halted whenmeningoenchephalitis developed in 6%of the study population. The mechanism of lymphocytemigration to the Alzheimer's brain and the effects of theselymphocytes in the parenchymal tissue have not beencharacterized. Here, we show that a single Aβ immunizationof old mice with Alzheimer's-like disease resulted in traffick-ing of T lymphocytes to parenchymal regions where Aβ hadaccumulated. The migration of the T lymphocytes across theglia limitans took place primarily from microvasculatureloaded with Aβ and populated with dendritic cells. Further-more, although mice were immunized once, Aβ T cellsinduced almost complete clearance of Aβ from the brain. Wesuggest that if properly regulated, the specific migration ofAβ Tcells to the brain may provide a novel drug delivery toolthat can be targeted and activated where Aβmanifests braintoxicity.

doi:10.1016/j.clim.2009.03.029

OR.23. TX527, a Less Calcemic Vitamin D Analogue,Directs Human T Cells to Sites of InflammationFemke Baeke, Evelyne van Etten, Chantal Mathieu. K.U.Leuven, Leuven, Belgium

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its lesscalcemic analogue TX527 are important immunomodula-tors, showing promising results in the prevention andtreatment of various animal models of autoimmunediseases. Lymphocyte trafficking represents a crucialphenomenon during inflammation and organ-specific auto-immunity. The aim of this study was to elucidate the role of1,25(OH)2D3 and analogues in lymphocyte trafficking.Human CD3+T-cells were activated by anti-CD3/anti-CD28.From day 2 onwards, T-cells were treated with TX527(10-8M) or vehicle (ethanol) every 2 days. On day 10,expression of chemokine-receptors and other homing-receptors was evaluated by flow cytometry. Skin-homingreceptors CCR4 and CCR10 were upregulated upon TX527-treatment (pb0,01), whereas expression of CLA wasdecreased (pb0,05). Gut-homing integrin-β7 was slightlysuppressed by TX527 (pb0,01), while CCR9-expressionremained unaffected. Importantly, TX527 reduced expressionof homeostatic lymph node homing-receptors (CD62L,CCR7,CXCR4;pb0,05), whereas chemokine-receptors involved inacute inflammation (CCR4,CXCR3,CXCR6;pb0,01) werestrongly increased. In conclusion, this study confirms thecapacity of 1,25(OH)2D3 and analogues to induce expressionof skin-homing receptors (CCR10), while suppressing recep-tors guiding T-cells to the gut (integrin-β7). Interestingly, theresults indicate that TX527 modulates expression of otherchemokine-and homing-receptors, creating a T-cell pheno-type with decreased homing capacities for secondarylymphoid organs, while increasing the ability to migrate tosites of inflammation. Our findings reveal a new mechanismunderlying the immunomodulatory actions of TX527 andcontribute to a better understanding of the mode of action of