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

Sara Abromson-Leeman, Rod Bronson, Yi Luo, Michael Berman, Rebecca Leeman, Joshua Leeman, Martin Dorf

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Two distinct clinical phenotypes of experimental autoimmune encephalomyelitis are observed in BALB interferon-γ 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 naïve 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-γ-deficient T cells that induce disease in the absence of both interferon-γ and neutrophils. These results highlight the multiplicity of T-cell-initiated effector pathways available for inflammation and demyelination.

Original languageEnglish
Pages (from-to)1519-1533
Number of pages15
JournalAmerican Journal of Pathology
Volume165
Issue number5
DOIs
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Dive into the research topics of 'T-cell properties determine disease site, clinical presentation, and cellular pathology of experimental autoimmune encephalomyelitis'. Together they form a unique fingerprint.

Cite this