title: Microbial infection-induced expansion of effector T cells overcomes the suppressive effects of regulatory T cells via an IL-2 deprivation mechanism.
abstract: Foxp3(+) regulatory T (Treg) 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 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.
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Benson
authors.forename: Sean
authors.initials: S
authors.lastname: Murray
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Divakar
authors.forename: Nikolay
authors.initials: N
authors.lastname: Burnaevskiy
authors.forename: Reed
authors.initials: R
authors.lastname: Pifer
authors.forename: James
authors.initials: J
authors.lastname: Forman
authors.forename: Felix
authors.initials: F
authors.lastname: Yarovinsky
mesh_terms: D000208:Acute Disease; D000818:Animals; D018791:CD4 Lymphocyte Count; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000172:deficiency* / Q000502:physiology; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D014615:Vaccinia / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2