A role for surface lymphotoxin in experimental autoimmune encephalomyelitis independent of LIGHT
| Autor: | Cheryl Nickerson-Nutter, Irene Sizing, Jeffrey L. Browning, Stuart J. Perper, Apinya Ngam-ek, Jennifer L. Gommerman, Keith Giza |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Lymphotoxin alpha
Tumor Necrosis Factor Ligand Superfamily Member 14 Encephalomyelitis Autoimmune Experimental Encephalomyelitis T cell T-Lymphocytes Priming (immunology) Biology Pertussis toxin Article Mice medicine Leukocytes Animals Receptor Lymphotoxin-alpha Mice Inbred BALB C Tumor Necrosis Factor-alpha Experimental autoimmune encephalomyelitis Brain Membrane Proteins General Medicine medicine.disease Rats Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Lymphotoxin Rats Inbred Lew Immunology Female |
| Zdroj: | The Journal of clinical investigation. 112(5) |
| ISSN: | 0021-9738 |
| Popis: | In studies using genetically deficient mice, a role for the lymphotoxin (LT) system in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has remained controversial. Here, we have reassessed this conclusion by using a fusion protein decoy that blocks the LT pathway in vivo without evoking the developmental defects inherent in LT-deficient mice. We have found that inhibition of the LT pathway prevented disease in two models of EAE that do not rely on the administration of pertussis toxin. Surprisingly, disease attenuation was due to specific blockade of LTalphabeta binding rather than the binding of LIGHT to its receptors. In a third system that requires pertussis toxin, LT inhibition did not affect disease, as was observed when the same model was used with LT-deficient mice. Disease prevention in pertussis toxin-free models was associated with defects in T cell responses and migration. When the DO11.10 T cell transgenic system was used, inhibition of the LT pathway was shown to uncouple T cell priming from T cell recall responses. Therefore, it is hypothesized that the LT pathway and its ability to maintain lymphoid microenvironments is critical for sustaining late-phase T cell responses in multiple sclerosis. |
| Databáze: | OpenAIRE |
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