Experimental expansion of the regulatory T cell population increases resistance to African trypanosomiasis

Abstract

Inflammatory responses mounted to eliminate parasites can be lethal if not counterbalanced by regulatory responses protecting the host from collateral tissue damage. Here, we show that the maintained inflammation associated with tissue damage, anemia, and reduced survival of Trypanosoma brucei-infected mice correlates with the absence of the expansion of the regulatory T (T reg) cell population. Induction of Treg cell expansion via CD28 superagonist antibody treatment in these mice down-regulated interferon-γ production by T cells and tumor necrosis factor-α and reactive oxygen species production by classically activated macrophages, triggered the development of alternatively activated macrophages, delayed the onset of liver injury, diminished the anemia burden, and prolonged the survival of infected animals. Thus, triggering the expansion of the Treg cell population coupled with the induction of alternatively activated macrophages can restore the balance between pro- and anti-inflammatory signals and thereby limit the pathogenicity of African trypanosomiasis. © 2008 by the Infectious Diseases Society of America. All rights reserved.