IL-10 balances proinflammatory immune regulation against the stimulation of CD8+ T-cell–mediated immunity and immunoglobulin G (IgG) production in B cells. In the absence of IL-10 receptors, patients with very-early-onset IBD suffer from severe childhood colitis. The absence of CD8+ T-cell–mediated immunosurveillance leads to the development of diffuse large B cell lymphomas.