Experimental autoimmune encephalomyelitis: Cytokines, effector t cells, and antigen-presenting cells in a prototypical th1-mediated autoimmune disease

2003 ◽  
Vol 3 (1) ◽  
pp. 86-93 ◽  
Author(s):  
Benjamin M. Segal
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Antigen Presenting Cells ◽  
Effector T Cells ◽  
Autoimmune Encephalomyelitis ◽  
Antigen Presenting ◽  
Experimental Autoimmune

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 Infection with Mycobacterium bovis BCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis

2003 ◽  
Vol 10 (4) ◽  
pp. 564-572 ◽  
Author(s):  
Diane L. Sewell ◽  
Emily K. Reinke ◽  
Dominic O. Co ◽  
Laura H. Hogan ◽  
Robert B. Fritz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Autoimmune Disease ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Mycobacterium Bovis ◽  
Clinical Severity ◽  
Dependent Manner ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

ABSTRACT Infectious agents have been proposed to influence susceptibility to autoimmune diseases such as multiple sclerosis. We induced a Th1-mediated central nervous system (CNS) autoimmune disease, experimental autoimmune encephalomyelitis (EAE) in mice with an ongoing infection with Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) to study this possibility. C57BL/6 mice infected with live BCG for 6 weeks were immunized with myelin oligodendroglial glycoprotein peptide (MOG35-55) to induce EAE. The clinical severity of EAE was reduced in BCG-infected mice in a BCG dose-dependent manner. Inflammatory-cell infiltration and demyelination of the spinal cord were significantly lessened in BCG-infected animals compared with uninfected EAE controls. ELISPOT and gamma interferon intracellular cytokine analysis of the frequency of antigen-specific CD4+ T cells in the CNS and in BCG-induced granulomas and adoptive transfer of MOG35-55-specific green fluorescent protein-expressing cells into BCG-infected animals indicated that nervous tissue-specific (MOG35-55) CD4+ T cells accumulate in the BCG-induced granuloma sites. These data suggest a novel mechanism for infection-mediated modulation of autoimmunity. We demonstrate that redirected trafficking of activated CNS antigen-specific CD4+ T cells to local inflammatory sites induced by BCG infection modulates the initiation and progression of a Th1-mediated CNS autoimmune disease.

scholarly journals Modulating lung immune cells by pulmonary delivery of antigen-specific nanoparticles to treat autoimmune disease

2020 ◽  
Vol 6 (42) ◽  
pp. eabc9317
Author(s):  
Eiji Saito ◽  
Stephen J. Gurczynski ◽  
Kevin R. Kramer ◽  
Carol A. Wilke ◽  
Stephen D. Miller ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Costimulatory Molecule ◽  
Substantial Reduction ◽  
Pulmonary Delivery ◽  
Autoimmune Encephalomyelitis ◽  
Intratracheal Administration ◽  
The Central Nervous System ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Antigen-specific particles can treat autoimmunity, and pulmonary delivery may provide for easier delivery than intravenous or subcutaneous routes. The lung is a “hub” for autoimmunity where autoreactive T cells pass before arriving at disease sites. Here, we report that targeting lung antigen-presenting cells (APCs) via antigen-loaded poly(lactide-co-glycolide) particles modulates lung CD4+ T cells to tolerize murine experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Particles directly delivered to the lung via intratracheal administration demonstrated more substantial reduction in EAE severity when compared with particles delivered to the liver and spleen via intravenous administration. Intratracheally delivered particles were associated with lung APCs and decreased costimulatory molecule expression on the APCs, which inhibited CD4+ T cell proliferation and reduced their population in the central nervous system while increasing them in the lung. This study supports noninvasive pulmonary particle delivery, such as inhalable administration, to treat autoimmune disease.

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