T cell-mediated autoimmune diseases can be caused by Th1 and/or Th17-type pathogenic T cells. However, whether these two pathogenic T cell subsets are driven by distinctive pathogenic factors and whether treatments found effective for Th1 responses have a similar effect on the Th17 responses remain unknown. We made a systematic comparison of these two pathogenic responses by identifying factors that promote or inhibit either response and by determining the responses to such treatments. Our results demonstrate that the two types of pathogenic response differ fundamentally in pathological progressions and in their susceptibility to treatments. Extracellular adenosine is a critical pathogenic molecule involved in the pathogenicity of inflammation and T cell reactivity. Here we show that aberrant adenosine production plays a major role in augmented Th17 responses in the pathogenesis of autoimmune diseases. The possibility that the potential effect of targeting adenosine or adenosine receptors as an effective approach to modulate pathogenic Th17 responses in autoimmune disease is discussed.