Download Jack Antel

Jack Antel
Professor; Dept. of Neurology
and Neurosurgery
Immune regulation and brain-immune interactions, autoimunity and
multiple sclerosis
Department of Neurology and Neurosurgery
Montreal Neurological Institute
3801 University, Room 111
Montreal, QC H3A 2B4
Tel: (514) 398-8531
Fax: (514) 398-7371
Email
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.
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.
Specific questions being studied are:
1. What effects the endogenous glial cells of the CNS (astrocytes, microglia) have on T
cells which infiltrate this compartment?
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.
2. What effects infiltrating T cells have on the endogenous glial cells?
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.
3. How do infiltrating T cells and activated glia contribute to the actual tissue injury as
occurs in neurologic diseases?
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 Recent Publications
Alter A, Duddy M, Hebert S, Biernacki K, Prat A, Antel JP, Yong VW, Nuttall RK,
Pennington CJ, Edwards DR, Bar-Or A. "Determinants of human B cell migration
across brain endothelial cells." J Immunol. 2003; 170(9):4497-505.
Seguin R, Biernacki K, Prat A, Wosik K, Kim HJ, Blain M, McCrea E, Bar-Or A,
Antel JP. "Differential effects of Th1 and Th2 lymphocyte supernatants on human
microglia." Glia. 2003; 42(1):36-45.
Seguin R, Biernacki K, Rotondo RL, Prat A, Antel JP. "Regulation and functional
effects of monocyte migration across human brain-derived endothelial cells." J
Neuropathol Exp Neurol. 2003; 62(4):412-9.
Seguin R, Moditi Z, Rotondo R, Biernacki K, Wosik K, Prat A, Antel JP. "Human
brain endothelial cells supply support for monocyte immunoregulatory functions." J
Neuroimmunol. 2003; 135(1-2):96-106.
Kim HJ, Antel JP, Duquette P, Alleva DG, Conlon PJ, Bar-Or A. "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.
Santos AC, Narayanan S, de Stefano N, Tartaglia MC, Francis SJ, Arnaoutelis R,
Caramanos Z, Antel JP, Pike GB, Arnold DL. "Magnetization transfer can predict
clinical evolution in patients with multiple sclerosis." J Neurol. 2002; 249(6):662-8.
Chakfe Y, Seguin R, Antel JP, Morissette C, Malo D, Henderson D, Seguela P. "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.
Prat A, Biernacki K, Lavoie JF, Poirier J, Duquette P, Antel JP. "Migration of
multiple sclerosis lymphocytes through brain endothelium." Arch Neurol. 2002
Mar;59(3):391-7.
Biernacki K, Prat A, Blain M, Antel JP. "Regulation of Th1 and Th2 lymphocyte
migration by human adult brain endothelial cells." J Neuropathol Exp Neurol. 2001
Dec;60(12):1127-36
Soos JM, Krieger JI, Stuve O, King CL, Patarroyo JC, Aldape K, Wosik K, Slavin
AJ, Nelson PA, Antel JP, Zamvil SS. "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.
Narayanan S, De Stefano N, Francis GS, Arnaoutelis R, Caramanos Z, Collins DL,
Pelletier D, Arnason BGW, Antel JP, Arnold DL. "Axonal metabolic recovery in
multiple sclerosis patients treated with interferon beta-1b." J Neurol. 2001
Nov;248(11):979-86.