title: Basophils inhibit proliferation of CD4⁺ T cells in autologous and allogeneic mixed lymphocyte reactions and limit disease activity in a murine model of graft versus host disease.
abstract: Basophils are known to modulate the phenotype of CD4(+) T cells and to enhance T helper type 2 responses in vitro and in vivo. In this study, we demonstrate that murine basophils inhibit proliferation of CD4(+) T cells in autologous and allogeneic mixed lymphocyte reactions. The inhibition is independent of Fas and MHC class II, but dependent on activation of basophils with subsequent release of interleukin-4 (IL-4) and IL-6. The inhibitory effect of basophils on T-cell proliferation can be blocked with antibodies against IL-4 and IL-6 and is absent in IL-4/IL-6 double-deficient mice. In addition, we show that basophils and IL-4 have beneficial effects on disease activity in a murine model of acute graft-versus-host disease (GvHD). When basophils were depleted with the antibody MAR-1 before induction of GvHD, weight loss, GvHD score, mortality and plasma tumour necrosis factor levels were increased while injection of IL-4 improved GvHD. Basophil-depleted mice with GvHD also have increased numbers of CD4(+) T cells in the mesenteric lymph nodes. Our data show for the first time that basophils suppress autologous and allogeneic CD4(+) T-cell proliferation in an IL-4-dependent manner.
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Fabian J
authors.initials: FJ
authors.lastname: Hermann
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez Gomez
authors.forename: Kristina
authors.initials: K
authors.lastname: Doser
authors.forename: Matthias
authors.initials: M
authors.lastname: Edinger
authors.forename: Petra
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Gabriela
authors.initials: G
authors.lastname: Schiechl
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Talke
authors.forename: Nicole
authors.initials: N
authors.lastname: Göbel
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schmidbauer
authors.forename: Shahzad N
authors.initials: SN
authors.lastname: Syed
authors.forename: Hilke
authors.initials: H
authors.lastname: Brühl
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
mesh_terms: D064591:Allografts; D000818:Animals; D064592:Autografts; D001491:Basophils / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
chemical_list: D016207:Cytokines
keywords: CD4+ T cells; basophils; graft-versus-host disease; interleukin-4; interleukin-6; mixed lymphocyte reaction