caa a22 4500 475748484 CHVBK 20180406123520.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1023/A:1006676315093 doi (NATIONALLICENCE)springer-10.1023/A:1006676315093 T-Cell Activation and Differentiation Are Regulated by TNF During Murine DBA/2 → B6D2F1 Intestinal Graft-Versus-Host Disease [Elektronische Daten] [Geri Brown, Dwain Thiele] Administration of a tumor necrosis factor (TNF) inhibitor-encoding adenoviral vector decreases the severity of colonic inflammation in a DBA/2→B6D2F1 murine model of colonic graft-versus-host disease (GVHD). The present studies evaluated the effect of TNF blockade on the splenic and colonic T-cell responses. cDNA encoding an artificial fusion protein consisting of the extracellular domain of the human 55-kDa receptor for TNF fused to a mouse IgG heavy chain was subcloned into an E1a-deficient adenoviral vector. Following transfer of DBA/2 T cells and bone marrow cells into irradiated B6D2F1 mice, the mice then received either the control adenovirus or the TNF inhibitor-encoding adenovirus. Splenic and colonic lymphocytes were isolated, stained with anti-H-2b, anti-H-2d, anti-CD3, anti-CD4, anti-CD8, and anti-CD45RB antibodies, and analyzed by flow cytometry. Splenic and colonic lymphocyte cytokine profiles also were assessed. More colonic T cells of donor origin were isolated from the control adenovirus recipients than from recipients of the TNF inhibitor encoding adenovirus (P = .027). Fewer CD4+ and CD8+ T cells were observed in colon but not in the spleen in the TNF inhibitor recipients. Fewer CD45RBlow(memory) T cells were observed in the CD4+ colonic lymphocytes isolated from the TNF inhibitor recipients than from controls. Importantly, lower levels of interleukin-2(IL-2) and interferon-gamma (INF-γ) but not of IL-4 were observed in the lamina propria lymphocyte RNA isolated from the TNF inhibitor recipients. Infiltration and expansion of donor T cells and T-cell activation in the colon appear to be regulated by TNF during murine DBA/2 → B6D2F1 gut GVHD. Plenum Publishing Corporation, 2000 TNF nationallicence GVHD nationallicence cytokine nationallicence T-cell nationallicence Brown Geri Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas aut Thiele Dwain Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas aut Journal of Clinical Immunology Kluwer Academic Publishers-Plenum Publishers 20/5(2000-09-01), 379-388 0271-9142 20:5<379 2000 20 10875 https://doi.org/10.1023/A:1006676315093 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1006676315093 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Brown Geri Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas aut NATIONALLICENCE 700 1- Thiele Dwain Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas aut NATIONALLICENCE 773 0- Journal of Clinical Immunology Kluwer Academic Publishers-Plenum Publishers 20/5(2000-09-01), 379-388 0271-9142 20:5<379 2000 20 10875 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer