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.
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]