Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells

2004 ◽  
Vol 10 (6) ◽  
pp. 651-659 ◽  
Author(s):  
Hideki Kato ◽  
Atsushi Ito ◽  
Jun Kawanokuchi ◽  
Shijie Jin ◽  
Tetsuya Mizuno ◽  
...  
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Adenylate Cyclase ◽  
Ex Vivo ◽  
Antigen Presenting Cells ◽  
Significant Inhibition ◽  
Autoimmune Encephalomyelitis ◽  
Pituitary Adenylate Cyclase ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Pituitary adenylate cyclase-activating polypeptide (PACAP), a 38-amino acid neuropeptide belonging to the secretin-glucagon-vasoactive intestinal peptide (VIP) family, performs a variety of functions in both the nervous and immune systems. In this study, we examined the effects of PACAP on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. When administrated intraperitoneally every other day after immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35 -55, PACAP ameliorated both the clinical and pathological manifestations of EAE. Ex vivo examination revealed a significant inhibition of MOG35 55-specific Th1 response in mice treated with PACAP.In vitro analysis revealed that PACAP suppressed the production of inflammatory cytokines, including TNF-a, IL-1b, and IL-12, and expression of the costimulatory factor B7-2 on macrophage and microglia, which may function as antigen presenting cells (APC) in the CNS. While PACAP suppressed the differentiation of MOG35 55-specific T cells into Th1 effectors upon restimulation with MOG35 55-expressing APC, it did not affect interferon (IFN)-g production by MOG35 55-specific T cells stimulated with anti-CD3 and anti-CD28. These observations suggested that PACAP suppressed induction of EAE primarily via suppression of APC function and inflammatory cytokine production. PACAP may be useful in the future treatment of Th1-mediated autoimmune diseases, such as multiple sclerosis.

scholarly journals Infusion of Sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate-Conjugated MOG35–55-Coupled Spleen Cells Effectively Prevents and Reverses Experimental Autoimmune Encephalomyelitis in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Lanfang Zhang ◽  
Yixian Guo ◽  
Chang-Qing Xia
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Cd4 T Cells ◽  
Ex Vivo ◽  
Th1 Cells ◽  
Spleen Cells ◽  
Control Groups ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

In this study, we have evaluated our recently developed method for antigen-cell coupling using sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate (sulfo-SMCC) heterobifunctional crosslinker in prevention and reversal of experimental autoimmune encephalomyelitis (EAE). We demonstrate that infusion of MOG35–55-coupled spleen cells (MOG-SP) significantly prevents and reverses EAE. Further studies show that the protected animals exhibit significantly delayed EAE upon EAE reinduction. Moreover, adoptive transfer of CD4+ T cells from the protected mice to naïve syngeneic mice renders the recipient mice resistant to EAE induction. Unexpectedly, CD4+ T cell proliferation is similar upon ex vivo stimulation by MOG35–55amongst all groups. However, further analysis of those proliferating CD4+ T cells shows remarkable differences in Foxp3+ regulatory T cells (70% in MOG-SP groups versus 10–25% in control groups) and in IL-17+ cells (2-3% in MOG-SP groups versus 6–9% in control groups). In addition, we discover that MOG-SP treatment also significantly attenuates MOG35–55-responding IFN-γ-producing Th1 cells. These findings suggest that MOG-SP treatment induces EAE protective MOG35–55-specific regulatory T cells and suppresses EAE pathogenic Th17 and Th1 cells. Our study provides a novel approach for antigen-based EAE immunotherapy, which can potentially be translated into clinical application for immunotherapy of multiple sclerosis.

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