平特五不中

Jack P Antel

Academic title(s): 

Professor


Neurology听and Neurosurgery

Jack P Antel
Contact Information
Address: 

Montreal Neurological Institute
3801 University, Rm 111
Montreal, QC H3A 2B4
Tel: (514) 398-1344
Fax: (514) 398-7371

Phone: 
514-398-7288
514-398-1931 Ext Clinic
Email address: 
jack.antel [at] mcgill.ca
Division: 
Associate Members
Branch: 
Immunology, Autoimmunity, Host Defense
Location: 
Montreal Neurological Institute
Current research: 

Research Interests

Immune regulation and brain-immune interactions, autoimunity and multiple sclerosis

Research Orientations

Our studies focus on the mechanisms underlying the interactions between the immune system and central nervous system (CNS) and how such interactions contribute to the tissue injury observed in such human neurologic disorders as multiple sclerosis, HIV encephalopathy, and Alzheimer's disease.听The studies are conducted using human peripheral blood derived immune cells and human neural cells (astrocytes, microglia, oligodendrocytes (OLs)), derived from surgically resected adult human CNS tissues.听

Specific questions being studied are:听

1. What effects the endogenous glial cells of the CNS (astrocytes, microglia) have on T cells which infiltrate this compartment?听
Continued recruitment and activation of Glial cells can serve as antigen presenting cells (APCs) to T cells but whether they promote or inhibit T cell responses seems dependent on the production of specific cytokines and expression of surface co-stimulatory molecules by the glial cells. By defining the precise properties of human adult glial cells which determine their APC capacities, we hope to learn how to modulate these functions for therapeutic purposes.听


2.听What effects infiltrating T cells have on the endogenous glial cells?听
How will the array of soluble and cell surface molecules expressed by T cells modulate the properties of the glial cells? Our specific approaches are to determine whether T cells induced in vivo (patients receiving immunomotherapies) or in vitro to express distinct cytokine profiles differentially effect glial cell functions and to selectively interfere with molecules mediating T cell-glial interactions using specific antibodies or receptor antagonists. Most of the latter reagents are being considered for clinical trials.听

3.How do infiltrating T cells and activated glia contribute to the actual tissue injury as occurs in neurologic diseases?听
Such injury selectively directed at myelinating cells (OLs) is regarded as the primary mechanism of injury in multiple sclerosis. A specific focus of our work is what cell surface or intra cellular properties of the OLs determines their apparent selective vulnerability to injury mediated via the tumor necrosis factor (TNF) receptor (R) superfamily (fas, TNF-R, p75 nerve growth factor R). Products of activated microglia and astrocytes are implicated as secondary mediators of neuronal injury in Alzheimer's disease and AIDs encephalopathy.

Selected publications: 
  • "Determinants of human B cell migration across brain endothelial cells." J Immunol. 2003; 170(9):4497-505.
  • "Differential effects of Th1 and Th2 lymphocyte supernatants on human microglia." Glia. 2003; 42(1):36-45.
  • "Regulation and functional effects of monocyte migration across human brain-derived endothelial cells." J Neuropathol Exp Neurol. 2003; 62(4):412-9.
  • "Human brain endothelial cells supply support for monocyte immunoregulatory functions." J Neuroimmunol. 2003; 135(1-2):96-106.
  • "Persistence of immune responses to altered and native myelin antigens in patients with multiple sclerosis treated with altered peptide ligand." Clin Immunol. 2002; 104(2):105-14.
  • "Magnetization transfer can predict clinical evolution in patients with multiple sclerosis." J Neurol. 2002; 249(6):662-8.
  • "ADP and AMP induce interleukin-1beta release from microglial cells through activation of ATP-primed P2X7 receptor channels." J Neurosci. 2002 Apr 15;22(8):3061-9.
  • "Migration of multiple sclerosis lymphocytes through brain endothelium." Arch Neurol. 2002 Mar;59(3):391-7.
  • "Regulation of Th1 and Th2 lymphocyte migration by human adult brain endothelial cells." J Neuropathol Exp Neurol. 2001 Dec;60(12):1127-36
  • "Malignant glioma cells use MHC class II transactivator (CIITA) promoters III and IV to direct IFN-gamma-inducible CIITA expression and can function as nonprofessional antigen presenting cells in endocytic processing and CD4(+) T-cell activation." Glia 2001 Dec;36(3):391-405.
  • "Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b." J Neurol. 2001 Nov;248(11):979-86.
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