009 – Implication of Cellular Adhesion Molecules (CAMs) in oligodendrocytes – CD4 T cells interaction

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009 – Implication of Cellular Adhesion Molecules (CAMs) in oligodendrocytes – CD4 T cells interaction

Helene JAMANN (1) – Qiao-Ling Cui (2) – Florian Pernin (2) – Victoria Hannah Mamane (2) – Oumarou Ouédraogo (1) – Audrey Daigneault (1) – Stefan Bittner (3) – Frauke Zipp (3) – Jack Antel (2) – Catherine Larochelle (1)
CRCHUM, Neurosciences, Montreal, Canada (1) – MNI, Neurosciences, Montreal, Canada (2) – Universitätsmedizin Mainz, Neuroimmunology, Mainz, Germany (3)


Introduction: The mechanisms driving oligodendrocyte (OL)/myelin sheath injury in MS are only partially understood and no neuroprotective therapeutic strategy is available. Proinflammatory CD4 T cells are pivotal immune mediators in MS and experimental autoimmune encephalitis (EAE). Activated CD4 T cells can exert cytotoxicity towards OLs in vitro and their presence impairs remyelination in vivo. Using two-photon live imaging in EAE, we observed direct interactions between activated CD4 T cells and OLs in vivo. As OLs do not express MHCII, the molecular mechanisms underlying these interactions are unknown. CD4 T cells found in MS brains express high levels of specific cell adhesion molecules (CAMs) and CAM ligands (CAMLs). We hypothesize that OLs express the cognate ligands of these CAMs/CAMLs in inflammatory conditions such as MS and EAE and that this CAMs/CAMLs interaction leads to OLs injury.
Objective: To characterize CAMs expression by human and mouse OLs in resting vs. inflamed conditions.
Methods: CAMs expression was measured by flow cytometry (FACS) on human OLs isolated ex vivo from MS vs control CNS tissue and by immunofluorescence on human MS vs control brain frozen sections in situ. Adult human OLs in primary culture were exposed to T cell-related cytokines, polarized T cells or activated CD4 T cells from MS versus healthy donors in vitro before assessment of CAMs expression by FACS, immunofluorescence and qRT-PCR. Functional impact of Th17 cells contact with OLs was assessed using co-culture assays.
Results: Adult human OLs express MCAM, ALCAM and ICAM-1. Expression of CAMs, especially ICAM-1, is higher on human OLs isolated from MS lesion than control CNS ex vivo. Co-expression of CAMs by OLs (NogoA/CC1) is observed in MS sections in situ. Exposure to TNF-alpha and/or IFN-gamma or coculture with activated T cells increases CAMs expression by human OLs in vitro. Moreover, contact with activated Th17 cells increases the percentage of human OLs death, damages myelin processes of remaining OLs and reduces their expression of CD200. Finally, our preliminary results suggest that activated CD4 T cells from MS patients show higher cytoxicity to OLs than CD4 T cells from healthy control.
Conclusion: CAMs expression is modulated by inflammatory conditions, suggesting that CAMs/CAMLs interactions could play a role in CD4 T cell mediated OLs injury in MS. Functional studies will evaluate the impact of blocking/depleting CAMs on OLs in neuroinflammation.