| First Author | Li X | Year | 2013 |
| Journal | Immunology | Volume | 138 |
| Issue | 3 | Pages | 208-15 |
| PubMed ID | 23121407 | Mgi Jnum | J:198090 |
| Mgi Id | MGI:5495379 | Doi | 10.1111/imm.12029 |
| Citation | Li X, et al. (2013) Pre-existing central nervous system lesions negate cytokine requirements for regional experimental autoimmune encephalomyelitis development. Immunology 138(3):208-15 |
| abstractText | In region-specific forms of experimental autoimmune encephalomyelitis (EAE), lesion initiation is regulated by T-cell-produced interferon-gamma (IFN-gamma) resulting in spinal cord disease in the presence of IFN-gamma and cerebellar disease in the absence of IFN-gamma. Although this role for IFN-gamma in regional disease initiation is well defined, little is known about the consequences of previous tissue inflammation on subsequent regional disease, information vital to the development of therapeutics in established disease states. This study addressed the hypothesis that previous establishment of regional EAE would determine subsequent tissue localization of new T-cell invasion and associated symptoms regardless of the presence or absence of IFN-gamma production. Serial transfer of optimal or suboptimal doses of encephalitogenic IFN-gamma-sufficient or -deficient T-cell lines was used to examine the development of new clinical responses associated with the spinal cord and cerebellum at various times after EAE initiation. Previous inflammation within either cerebellum or spinal cord allowed subsequent T-cell driven inflammation within that tissue regardless of IFN-gamma presence. Further, T-cell IFN-gamma production after initial lesion formation exacerbated disease within the cerebellum, suggesting that IFN-gamma plays different roles at different stages of cerebellar disease. For the spinal cord, IFN-gamma-deficient cells (that are ordinarily cerebellum disease initiators) were capable of driving new spinal-cord-associated clinical symptoms more than 60 days after the initial acute EAE resolution. These data suggest that previous inflammation modulates the molecular requirements for new neuroinflammation development. |
