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Role of Neuronal Interferon-γ in the Development of Myelopathy in Rats Infected with Human T-Cell Leukemia Virus Type 1
- Source :
- The American Journal of Pathology. 169:189-199
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of not only adult T-cell leukemia but also HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Among the rat strains infected with HTLV-1, chronic progressive myelopathy, named HAM rat disease, occurs exclusively in WKAH rats. In the present study, we found that HTLV-1 infection induces interferon (IFN)-gamma production in the spinal cords of HAM-resistant strains but not in those of WKAH rats. Neurons were the major cells that produced IFN-gamma in HTLV-1-infected, HAM-resistant strains. Administration of IFN-gamma suppressed expression of pX, the gene critically involved in the onset of HAM rat disease, in an HTLV-1-immortalized rat T-cell line, indicating that IFN-gamma protects against the development of HAM rat disease. The inability of WKAH spinal cord neurons to produce IFN-gamma after infection appeared to stem from defects in signaling through the interleukin (IL)-12 receptor. Specifically, WKAH-derived spinal cord cells were unable to up-regulate the IL-12 receptor beta2 gene in response to IL-12 stimulation. We suggest that the failure of spinal cord neurons to produce IFN-gamma through the IL-12 pathway is involved in the development of HAM rat disease.
- Subjects :
- T-Lymphocytes
Molecular Sequence Data
Gene Expression
Enzyme-Linked Immunosorbent Assay
Spinal Cord Diseases
Cell Line
Pathology and Forensic Medicine
Interferon-gamma
Myelopathy
immune system diseases
Interferon
hemic and lymphatic diseases
Tropical spastic paraparesis
medicine
Animals
Interferon gamma
RNA, Messenger
Neurons
Human T-lymphotropic virus 1
Microscopy, Confocal
Base Sequence
biology
Reverse Transcriptase Polymerase Chain Reaction
Genes, pX
Receptors, Interleukin-12
Brain
virus diseases
Rats, Inbred Strains
Receptors, Interleukin
biology.organism_classification
medicine.disease
HTLV-I Infections
Interleukin-12
Rats
Disease Models, Animal
Leukemia
medicine.anatomical_structure
Spinal Cord
Immunology
Interleukin 12
Neuron
Regular Articles
medicine.drug
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 169
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....a468f3f1c0554291b7476be531a8ee5e
- Full Text :
- https://doi.org/10.2353/ajpath.2006.051225