title: 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.affiliation: Department of Pathology, Harvard Medical School, New Research Building, 77 Louis Pasteur Ave., Boston, MA 02115, USA. sara@abromson-leeman@hms.harvard.edu
authors.forename: Sara
authors.initials: S
authors.lastname: Abromson-Leeman
authors.forename: Rod
authors.initials: R
authors.lastname: Bronson
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Michael
authors.initials: M
authors.lastname: Berman
authors.forename: Rebecca
authors.initials: R
authors.lastname: Leeman
authors.forename: Joshua
authors.initials: J
authors.lastname: Leeman
authors.forename: Martin
authors.initials: M
authors.lastname: Dorf
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons; D005434:Flow Cytometry; D006579:Heterozygote; D006720:Homozygote; D007249:Inflammation; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012260:Ribonucleases / Q000378:metabolism; D013601:T-Lymphocytes / Q000473:pathology*; D013997:Time Factors
chemical_list: D016207:Cytokines; D004676:Myelin Basic Protein; D010455:Peptides; D007371:Interferon-gamma; D012260:Ribonucleases