title: Attenuation of graft-versus-host-disease in NOD scid IL-2Rγ(-/-) (NSG) mice by ex vivo modulation of human CD4(+) T cells.
abstract: NOD.Cg-Prkdc(scid) IL-2rg(tm1Wjl) /SzJ (NSG) mice are a valuable tool for studying Graft-versus-Host-Disease (GvHD) induced by human immune cells. We used a model of acute GvHD by transfer of human peripheral blood mononuclear cells (PBMCs) into NSG mice. The severity of GvHD was reflected by weight loss and was associated with engraftment of human cells and the expansion of leukocytes, particularly granulocytes and monocytes. Pre-treatment of PBMCs with the anti-human CD4 antibody MAX.16H5 IgG1 or IgG4 attenuated GvHD. The transplantation of 2 × 10(7) PBMCs without anti-human CD4 pre-treatment induced a severe GvHD (0% survival). In animals receiving 2 × 10(7) PBMCs pre-incubated with MAX.16H5 IgG1 or IgG4, GvHD development was reduced and survival was increased. Immune reconstitution was measured by flow cytometry and confirmed for human leukocytes (CD45), CD3(+) /CD8(+) cytotoxic T cells and CD3(+) /CD4(+) T helper cells. Human B cells (CD19) and monocytes (CD14) could not be detected. Histopathological analysis (TUNEL assay) of the gut of recipient animals showed significantly less apoptotic crypt cells in animals receiving a MAX.16H5 IgG1 pre-incubated graft. These findings indicate that pre-incubation of an allogeneic graft with an anti-human CD4 antibody may decrease the frequency and severity of GvHD after hematopoietic stem cell transplantation (HSCT) and the need of conventional immunosuppressive drugs. Moreover, this approach most probably provides a safer HSCT that must be confirmed in appropriate clinical trials in the future. © 2016 International Society for Advancement of Cytometry.
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Nadja
authors: N
authors: Hilger
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany. jakob.glaser@izi-extern.fraunhofer.de.
authors: Jakob
authors: J
authors: Glaser
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Claudia
authors: C
authors: Müller
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Christoph
authors: C
authors: Halbich
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Anne
authors: A
authors: Müller
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Ulla
authors: U
authors: Schwertassek
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Jörg
authors: J
authors: Lehmann
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Peter
authors: P
authors: Ruschpler
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Franziska
authors: F
authors: Lange
authors: Institute for Clinical Immunology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Andreas
authors: A
authors: Boldt
authors: Institute for Clinical Immunology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Lilly
authors: L
authors: Stahl
authors: Institute for Clinical Immunology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Ulrich
authors: U
authors: Sack
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Christopher
authors: C
authors: Oelkrug
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Frank
authors: F
authors: Emmrich
authors: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors: Stephan
authors: S
authors: Fricke
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D000906:Antibodies; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit
keywords: Graft-versus-Host-Disease; MAX.16H5 IgG1; MAX.16H5 IgG4; NSG mice; anti-human CD4 antibody; hematopoietic stem cell transplantation