Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Abstract

Ž .Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis MS and experimental autoimmune Ž . 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 Ž . 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 Ž . Ž . may result from local CD40-CD40L interactions. CD40 ligand CD40L and B7-2 CD86 were also expressed, but to a lower extent, Ž . while B7-1 CD80 expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual Ž . lesions during active disease IFN-a, IFN-g , TNF-a, IL-1a , IL-1b, 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. q

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

“…The immunohistochemical methods used in this study were described in detail before (18). In brief, 6-mm frozen sections of human brain white matter were thaw-mounted on gelatin-coated slides and kept overnight at room temperature (RT) in humidified atmosphere.…”

Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

“…Immunohistochemistry was performed as described [34,35]. Primary antibodies were polyclonal rabbit antibodies against transcription growth factor (TGF)-β (Santa Cruz) and NF-L (Abcam), and monoclonal mouse antibodies against NSE (MIG M3; Abcam), microtubule-associated protein-2 (MAP-2; HSM 5; Pierce Biotechnology), NF-H (SMI-32; Sternberger Monoclonals), PLP (J1/06 [36]), HLA-DP/DQ/DR (CR3/43; DAKO), CD40 (5D12; dr. M. de Boer), interleukin 1 receptor antagonist (IL-1ra; A71B6D11; Bioscource), tumor necrosis factor (TNF)-α (61E71; U Cytech), IL-12p40/p70 (C8.6; BD), and CCR7 (2H4; BD).…”

Dual Effect of Central Injection of Recombinant Rat Interleukin-4 on Lipopolysaccharide-Induced Sickness Behavior in Rats

“…Peripherally released cytokines act on the brain by inducing the expression and release of cytokines in the central nervous system (Eriksson et al 2000;Konsman et al 1999;Layé et al 2000;Quan et al 2000). LPS induces the expression of not only pro-inflammatory but also anti-inflammatory cytokines such as IL-10 and IL-13 in the brain (Wong et al 1997 Laman et al 1998;Liedtke et al 1998; Woodroofe and Cuzner 1993). Anti-inflammatory cytokines have the ability to suppress the synthesis of IL-1, TNF, and other cytokines in peripheral immune and non-immune cells (Dinarello 1997;Marie and Cavaillon 1997).…”

“…Another important antiinflammatory cytokine is IL-4. Although it is not syn-thesized in the normal brain (Lovett-Racke et al 2000;Schluter et al 1997), it is strongly expressed during brain injury, infection, experimental autoimmune encephalomyelitis, and neurodegenerative processes (Arsenijevic et al 1998;Laman et al 1998;Liedtke et al 1998;Woodroofe and Cuzner 1993). Anti-inflammatory cytokines have the ability to suppress the synthesis of IL-1, TNF, and other cytokines in peripheral immune and non-immune cells (Dinarello 1997;Marie and Cavaillon 1997).…”