Intercellular Adhesion Molecule-1 Expression Is Required on Multiple Cell Types for the Development of Experimental Autoimmune Encephalomyelitis

Abstract

Many members of the Ig superfamily of adhesion molecules, such as ICAM-1 and VCAM-1, have been implicated in the pathogenesis of multiple sclerosis. Although it is well-established that VCAM-1/VLA-4 interactions can play important roles in mediating CNS inflammatory events in multiple sclerosis patients and during the development of experimental allergic encephalomyelitis (EAE), the contributions of ICAM-1 are poorly understood. This is due in large part to conflicting results from Ab inhibition studies and the observation of exacerbated EAE in ICAM-1 mutant mice that express a restricted set of ICAM-1 isoforms. To determine ICAM-1-mediated mechanisms in EAE, we analyzed ICAM-1 null mutant mice (ICAM-1null), which express no ICAM-1 isoforms. ICAM-1null mice had significantly attenuated EAE characterized by markedly reduced spinal cord T cell infiltration and IFN-γ production by these cells. Adoptive transfer of Ag-restimulated T cells from wild-type to ICAM-1null mice or transfer of ICAM-1null Ag-restimulated T cells to control mice failed to induce EAE. ICAM-1null T cells also showed reduced proliferative capacity and substantially reduced levels of IFN-γ, TNF-α, IL-4, IL-10, and IL-12 compared with that of control T cells following myelin oligodendrocyte glycoprotein 35–55 restimulation in vitro. Our results indicate that ICAM-1 expression is critical on T cells and other cell types for the development of demyelinating disease and suggest that expression of VCAM-1 and other adhesion molecules cannot fully compensate for the loss of ICAM-1 during EAE development.

p150/95 (CD11c/CD18) Expression Is Required for the Development of Experimental Autoimmune Encephalomyelitis

“…Given the overlapping functions of Mac-1 and p150/95, deletion of both receptors may result in a complete inhibition of disease similar to that seen when their common ligand intercellular adhesion molecule-1 is deleted. 59 Thus, the ␤2-integrin family members, including p150/95, may offer new therapeutic approaches for demyelinating disease.…”

ICAM-1–dependent tuning of memory CD8 T-cell responses following acute infection

“…P14 TCR transgenic mice were bred in house. ICAM-1 −/− C57BL/6 mice (Icam1 tm1Alb ) have been described (16,17). CD2-ICAM-1/ICAM-1 −/− transgenic mice were generated as follows.…”

“…Several previous studies have harnessed ICAM-1-deficient mice with targeted deletions in exons 4 and 5, in which soluble or membrane-bound splice variants, respectively, may still be expressed (13)(14)(15), thus potentially complicating their interpretation. In the current report, we have used ICAM-1 −/− (Icam1 tm1A1b ) mice, in which the entire coding region of the ICAM1 gene has been deleted (16,17), as well as experimental systems in which ICAM-1 expression is restricted to specific cell types. Rather than a mandatory role for ICAM-1 in the development of CD8 T-cell memory, as suggested by peptide priming studies (3), we detect equivalent or enhanced generation and maintenance of memory-phenotype (CD127 hi , KLRG-1 lo ) CD8 T cells following acute lymphocytic choriomeningitis virus (LCMV) infection of ICAM-1 −/− mice.…”

Epigallocatechin-3-Gallate Ameliorates Experimental Autoimmune Encephalomyelitis by Altering Balance among CD4+ T-Cell Subsets

“…Adhesion molecules play an important role in the migration of immune cells into the CNS. Patients with MS have increased serum levels of soluble ICAM-1 (sICAM-1), 36,37 and recent studies 9,38 have shown that ICAM-1 is more important than other adhesion molecules in promoting pathological cell infiltration into the CNS and the development of EAE. To determine whether this molecule is involved in the EGCGinduced reduction of inflammatory infiltration, we measured the plasma sICAM-1 level and found that it was lower in mice fed EGCG compared with those fed the control diet ( Figure 9A).…”