T-cell properties determine disease site, clinical presentation, and cellular pathology of experimental autoimmune encephalomyelitis.

Abstract

Two distinct clinical phenotypes of experimental autoimmune encephalomyelitis are observed in BALB interferon-gamma knockout mice immunized with encephalitogenic peptides of myelin basic protein. Conventional disease, characterized by ascending weakness and paralysis, occurs with greater frequency after immunizing with a peptide comprising residues 59 to 76. Axial-rotatory disease, characterized by uncontrolled axial rotation, occurs with greater frequency in mice immunized with a peptide corresponding to exon 2 of the full length 21.5-kd protein. The two clinical phenotypes are histologically distinguishable. Conventional disease is characterized by inflammation and demyelination primarily in spinal cord, whereas axial-rotatory disease involves inflammation and demyelination of lateral medullary areas of brain. Both types have infiltrates in which neutrophils are a predominating component. By isolating T cells and transferring disease to naive recipients, we show here that the type of disease is determined entirely by the inducing T cell. Furthermore, studies using CXCR2 knockout recipients, unable to recruit neutrophils to inflammatory sites, show that although neutrophils are critical for some of these T cells to effect disease, there are also interferon-gamma-deficient T cells that induce disease in the absence of both interferon-gamma and neutrophils. These results highlight the multiplicity of T-cell-initiated effector pathways available for inflammation and demyelination.

• Authors: Sara Abromson-Leeman, Rod Bronson, Yi Luo, Michael Berman, Rebecca Leeman, Joshua Leeman, Martin Dorf
• Journal: The American journal of pathology (Am J Pathol) Vol. 165 Issue 5 Pg. 1519-33 (Nov 2004) ISSN: 0002-9440 [Print] United States
• PMID: 15509523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Myelin Basic Protein
• Peptides
• Interferon-gamma
• Ribonucleases

Topics

• Animals
• Antigen Presentation
• Cell Proliferation
• Central Nervous System (cytology)
• Cloning, Molecular
• Cytokines (metabolism)
• Encephalomyelitis, Autoimmune, Experimental (blood)
• Enzyme-Linked Immunosorbent Assay
• Exons
• Flow Cytometry
• Heterozygote
• Homozygote
• Inflammation
• Interferon-gamma (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Myelin Basic Protein (physiology)
• Neutrophils (metabolism)
• Peptides (chemistry)
• Phenotype
• Protein Structure, Tertiary
• Ribonucleases (metabolism)
• T-Lymphocytes (pathology)
• Time Factors