Microbial Infection-Induced Expansion of Effector T Cells Overcomes the Suppressive Effects of Regulatory T Cells via an IL-2 Deprivation Mechanism

J Immunol. 2011 Dec 5. [Epub ahead of print]

Microbial Infection-Induced Expansion of Effector T Cells Overcomes the Suppressive Effects of Regulatory T Cells via an IL-2 Deprivation Mechanism.

Benson A, Murray S, Divakar P, Burnaevskiy N, Pifer R, Forman J, Yarovinsky F.

SourceDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390.

Abstract
Regulatory Foxp3(+) T cells are a critical cell population that suppresses T cell activation in response to microbial and viral pathogens. We identify a cell-intrinsic mechanism by which effector CD4(+) T cells overcome the suppressive effects of regulatory T (Treg) cells in the context of three distinct infections: Toxoplasma gondii, Listeria monocytogenes, and vaccinia virus. The acute responses to the parasitic, bacterial, and viral pathogens resulted in a transient reduction in frequency and absolute number of Treg cells. The infection-induced partial loss of Treg cells was essential for the initiation of potent Th1 responses and host protection against the pathogens. The observed disappearance of Treg cells was a result of insufficiency in IL-2 caused by the expansion of pathogen-specific CD4(+) T cells with a limited capacity of IL-2 production. Exogenous IL-2 treatment during the parasitic, bacterial, and viral infections completely prevented the loss of Treg cells, but restoration of Treg cells resulted in a greatly enhanced susceptibility to the pathogens. These results demonstrate that the transient reduction in Treg cells induced by pathogens via IL-2 deprivation is essential for optimal T cell responses and host resistance to microbial and viral pathogens.

PMID:22147768[PubMed - as supplied by publisher]