Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus).
Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of marmoset monkeys (Callithrix jacchus) with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions may result from local CD40-CD40L interactions. CD40 ligand (CD40L) and B7-2 (CD86) were also expressed, but to a lower extent, while B7-1 (CD80) expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual lesions during active disease (IFN-alpha, IFN-gamma, TNF-alpha, IL-1alpha, IL-1beta, IL-2, IL-4, IL-10 and IL-12). This suggests that relative levels rather than sequential expression of Th1- and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention.
Laman
J D
JD
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands. jd.laman@pg.tno.nl
van Meurs
M
M
Schellekens
M M
MM
de Boer
M
M
Melchers
B
B
Massacesi
L
L
Lassmann
H
H
Claassen
E
E
Hart
B A
BA
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D001921:Brain / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001923:Brain Chemistry / Q000276:immunology*; D019013:CD40 Antigens / Q000032:analysis; D002144:Callithrix; D016207:Cytokines / Q000032:analysis*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016898:Interferon-alpha / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008264:Macrophages / Q000737:chemistry / Q000201:enzymology / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D016898:Interferon-alpha; D007375:Interleukin-1; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D000135:Acid Phosphatase