IL-10 is a critical anti-inflammatory cytokine, the deficiency of which leads to spontaneous autoimmunity. However, therapeutically administered or ectopically expressed IL-10 can either suppress or promote disease. Distinct lineage-specific activities may explain the contradictory effects of IL-10. To dissect the T cell-specific response to IL-10 during organ-specific autoimmunity, we generated mice with a selective deletion of IL-10R in T cells and analyzed its effects in an autoimmune model, experimental allergic encephalomyelitis (EAE). Surprisingly, the T cell response to IL-10 increased EAE severity. This did not result from altered T cell functional potential; T cell cytokine profile was preserved. IL-10 also diminished the proliferation of T cells in situ within the target organ, an effect that would be expected to restrain disease. However, IL-10 acted cell autonomously to sustain the autoreactive T cells essential for immunopathogenesis, promoting their accumulation and distorting the regulatory and effector T cell balance. Indeed, in chimeric mice and after adoptive transfer, wild type T cells showed a competitive advantage over cells deficient in IL-10R. Therefore, T cell specific actions of IL-10 can support autoimmune inflammation, and this appears to result from an overall increase in the long term fitness of pathologic T cells. Lineage-restricted, disease-promoting activities of IL-10 should be considered in the therapeutic manipulation of the IL-10 pathway.