2014/02/13 by Josa M. Frischer, Markus Reindl, Bettina Künz +6 · 4 citations
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · Medicine · #T-cell and B-cell Immunology #NF-κB Signaling Pathways #Cell death mechanisms and regulation #Multiple sclerosis #Cytokine #T cell #Inflammation #Myelin #Ex vivo #Experimental autoimmune encephalomyelitis #Myelin basic protein #Immunology #Immune system #Biology #In vivo #Medicine #Central nervous system #Endocrinology
paper · doi:10.1177/1352458514521516
published in Multiple Sclerosis Journal 20(9), 1171-1181 (SAGE Publishing)
openalex publication_date 2014/02/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/11
BACKGROUND AND OBJECTIVE: Interactions between TIRC7 (a novel seven-transmembrane receptor on activated lymphocytes) and its ligand HLA-DR might be involved in the inflammatory process in multiple sclerosis (MS). METHODS: Methods comprised immunohistochemistry and microscopy on archival MS autopsies, proliferation-, cytokine-, and surface-staining assays using peripheral blood lymphocytes (PBLs) from MS patients and an in vitro model. RESULTS: TIRC7 was expressed in brain-infiltrating lymphocytes and strongly correlated with disease activity in MS. TIRC7 expression was reduced in T cells and induced in B cells in PBLs obtained from MS patients. After ex vivo activation, T cell expression of TIRC7 was restored in patients with active MS disease. The interaction of TIRC7(+) T lymphocytes with cells expressing HLA-DR on their surface led to T cell proliferation and activation whereas an anti-TIRC7 mAb preventing interactions with its ligand inhibited proliferation and Th1 and Th17 cytokine expression in T cells obtained from MS patients and in myelin basic protein-specific T cell clone. CONCLUSION: Our findings suggest that TIRC7 is involved in inflammation in MS and anti-TIRC7 mAb can prevent immune activation via selective inhibition of Th1- and Th17-associated cytokine expression. This targeting approach may become a novel treatment option for MS.