Local delivery of TNF by retrovirus-transduced T lymphocytes exacerbates experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAP) is an inflammatory autoimmu ne disease of the central nervous system that serves as a model for the hum an disease multiple sclerosis. Paralysis is "induced" by CD4+ T cells of th e Th1 phenotype. Tumor necrosis factor (TNF), a Th1 type cytokine, has been shown to be upregulated in the CNS during the onset of EAE, and systemic m anipulations of TNF have had substantial effects on disease progression. Ho wever, the precise role of TNF in EAE has been called into question by rece nt experiments utilizing TNF and lymphotoxin knockout mice. We demonstrate here that the local delivery of TNF by myelin basic protein (MBP)-specific T cells, retrovirally transduced to express TNF, exacerbated MBP-induced di sease following adoptive transfer into syngeneic mice. (C) 1999 Academic Pr ess.