title: Endotoxin hyperresponsiveness upon CD4+ T cell reconstitution in lymphopenic mice: control by natural regulatory T cells.
abstract: Natural CD4(+)CD25(+) regulatory T cells (nTreg) have been shown to control graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). Herein, we considered the possibility that the beneficial action of nTreg upon immune reconstitution in lymphopenic hosts involves dampening of the inflammatory response induced by bacterial products. We first observed that transfer of syngeneic CD4(+)CD25(-) T cells in RAG-deficient mice dramatically enhanced release of inflammatory cytokines and associated pathology upon endotoxin injection. Interferon (IFN)-gamma produced by T cells undergoing homeostatic proliferation was shown to be involved in the endotoxin hyperresponsiveness induced by CD4(+) T cell reconstitution. Co-transfer of CD4(+)CD25(+) nTreg with CD4(+)CD25(-) T cells inhibited the expansion of IFN-gamma-producing T cells and reduced endotoxin responses in RAG(-/-) mice. We conclude that (1) CD4(+) T cell reconstitution sensitizes lymphopenic hosts to endotoxin-induced pathology and (2) nTreg prevent this process by limiting the emergence of IFN-gamma-producing cells.
authors: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors: Virginie
authors: V
authors: De Wilde
authors: Fleur Samantha
authors: FS
authors: Benghiat
authors: Magali
authors: M
authors: Novalrivas
authors: Jean-François
authors: JF
authors: Lebrun
authors: Carole
authors: C
authors: Kubjak
authors: Guillaume
authors: G
authors: Oldenhove
authors: Jean-Marc
authors: JM
authors: Verdebout
authors: Michel
authors: M
authors: Goldman
authors: Alain
authors: A
authors: Le Moine
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D004731:Endotoxins / Q000276:immunology*; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000235:genetics; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004731:Endotoxins; D018398:Homeodomain Proteins; D053645:Interleukin-2 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha; C064658:RAG-1 protein; D007371:Interferon-gamma