Macrophage brain infiltration in experimental autoimmune encephalomyelitis is not completely compromised by suppressed T-cell invasion: in vivo magnetic resonance imaging illustration in effective anti-VLA-4 antibody treatment.
Large inflammatory infiltrates of T cells, macrophages and B cells in the central nervous system (CNS) contribute to the pathogenesis of multiple sclerosis (MS). The passage of T cells through the blood-brain barrier can be suppressed with antibodies directed against alpha-4 integrins (VLA-4) that mediate T-cell adherence. This treatment, in phase III of clinical trial evaluation, reduces lesion development in MS patients. In the ongoing inflammatory disease process the consequences of T-cell inhibitory anti-VLA-4 antibodies on inflammatory compounds are still poorly investigated. We show that anti-VLA-4 antibody treatment during the late preclinical phase of the acute experimental autoimmune encephalomyelitis (EAE) MS rat model interrupts T-cell egress out of the vascular compartment and suppresses clinical disease and histological alterations but macrophage recruitment in the CNS is not fully compromised. Among the treated EAE animals not developing disease, none presented foci of T-cell infiltration in CNS. However, in 75% of the treated EAE rats monocyte ingress in CNS was observed in vivo by magnetic resonance imaging with the ultrasmall superparamagnetic iron oxide contrast agent. Our data shed new light on the role of remaining macrophage brain infiltration in an induced but interrupted T-cell-mediated EAE disease process.
EA 2966 Neurobiology of Myelin Diseases Laboratory, University Victor Segalen Bordeaux 2, Bordeaux, France.
Mathilde S A
MS
Deloire
Tarik
T
Touil
Bruno
B
Brochet
Vincent
V
Dousset
Jean-Marie
JM
Caillé
Klaus G
KG
Petry
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D003287:Contrast Media; D003545:Cysteine; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005290:Ferric Compounds; D039041:Integrin alpha4beta1 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D000069442:Natalizumab; D051381:Rats; D011917:Rats, Inbred Lew; D012710:Serum Albumin, Bovine; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D003287:Contrast Media; D000939:Epitopes; D005290:Ferric Compounds; D039041:Integrin alpha4beta1; D000069442:Natalizumab; C000499:ferric oxide; D012710:Serum Albumin, Bovine; D003545:Cysteine