Adhesion molecules in experimental autoimmune uveitis

AbstractPurpose Non infectious uveitis are characterized by the penetration of immune cells into the eye which depends on adhesion molecules expression on the blood retinal barrier (BRB). In this work, we have studied the expression of the adhesion molecules VCAM‐1 and ICAM‐1 in experimental autoimmune uveitis (EAU) by adoptive transfer and the expression of their ligands, VLA‐4 and LFA‐1, on autoreactive T‐lymphocyte (TL)Methods Autoreactive TL, obtained from the lymph node of C57BL6 mice immunized with IRBP 1‐20, were purified using CD4+ magnetic cell sorting. Those cells were studied by flow cytometry for their expression of VLA‐4 and LFA‐1. ELISAs and intracytoplasmic flow cytometry were performed to study the cytokine expression profile. Then, EAU were induced by adoptive transfer of those cells into naive mice. VCAM‐1 and ICAM‐1 histological and cellular expression was studied by immunofluorescence on eye cryosectionsResults Autoreactive TL were found to be from the Th1 and Th17 phenotypes. LFA‐1 was expressed on all T and non T cells and VLA‐4 mostly on non T cells. Only a minority of TL showed VLA‐4 expression. In the eye of naïve mice VCAM‐1 was absent and ICAM‐1 present only at very low level. VCAM‐1 and ICAM‐1 expression is correlated to the severity of the disease. Interestingly, VCAM‐1 was more expressed on the internal BRB and ICAM‐1 on the external BRBConclusion This work shows that the adhesion molecules VCAM‐1 and ICAM 1 were expressed differently on the internal and external BRB and that their respective ligands VLA‐4 and LFA‐1 were also expressed differently on lymphocytes. This works complete the understanding of the major role of the adhesion molecules VCAM‐1 and ICAM‐1 in the induction uveitis in the adoptive transfer model