Th17 cells mediate sustained autoimmune inflammation and are highly resistant to restimulation-induced cell death (137.17)

Abstract

Abstract Both Th1 and Th17 T-cell subsets can mediate inflammation, but the kinetics of the pathogenic process mediated by these two subsets has not been investigated. Using an experimental system in which TCR-transgenic Th1 or Th17 cells specific for hen egg lysozyme (HEL) induce ocular inflammation in recipient mice expressing eye-restricted HEL, we found important differences in the in vivo behavior of these two subsets. Th1 cells initially proliferated considerably faster and invaded the eye more quickly than their Th17 counterparts, but then disappeared rapidly. By contrast, Th17 cells accumulated and remained the majority of the infiltrating CD4 cells in the eye for at least 15 days after transfer, mediating more long-lasting pathological changes. Th17 cells were highly resistant to restimulation-induced apoptosis, a major pathway by which autoimmune and chronically restimulated Th1 cells are eliminated. Th17 cells had reduced FasL production and resistance to Fas-induced apoptosis relative to Th1 cells despite normal surface expression of Fas. Moreover, Th1 recipient eyes had a higher expression level of FasL than Th17 recipient eyes. Resistance to programmed cell death in Th17 cells may enable more long-lasting responses against pathogens, but may also enable the chronic autoimmune tissue destruction that has been ascribed to Th17 cells.