Expansion and Activation Kinetics of Immune Cells during Early Phase of GVHD in Mouse Model Based on Chemotherapy Conditioning

• Published in: Clinical & developmental immunology 2010-01, Vol.2010 (2010), p.1-13
• Main Authors: Abedi-Valugerdi, Manuchehr, Hassan, Moustapha, Sadeghi, Behnam, Grönvik, Kjell-Olov, Lundmark, Carin, Concha, Hernan, al-Hashmi, Suleiman, Hassan, Zuzana, Rozell, Bjorn
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Alkylating - pharmacology; Bone marrow; Busulfan - pharmacology; Cancer; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cyclophosphamide - pharmacology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Disease Models, Animal; Female; Graft vs Host Disease - immunology; Graft vs Host Disease - pathology; Hematopoietic Stem Cell Transplantation; Immunology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-2 - immunology; Interleukin-2 - metabolism; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Male; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Stem cells; Time Factors; Transplantation Conditioning - adverse effects; Transplantation, Homologous; Transplants & implants; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1740-2522; 2314-8861; 1740-2530; 1740-2530; 2314-7156
• DOI: 10.1155/2010/142943

In the present paper, we have investigated early pathophysiological events in graft-versus-host disease (GVHD), a major complication to hematopoietic stem cell transplantation (HSCT). BLLB/c female mice conditioned with busulfan/cyclophosphamide (Bu-Cy) were transplanted with allogeneic male C57BL/6. Control group consisted of syngeneic transplanted Balb/c mice. In allogeneic settings, significant expansion and maturation of donor dendritic cells (DCs) were observed at day +3, while donor T-cells CD8+ were increased at day +5 (230%) compared to syngeneic HSCT. Highest levels of inflammatory cytokines IL-2, IFN-gamma, and TNF-alfa at day +5 matched T-cell activation. Concomitantly naïve T-cells gain effecr-memory phenotype and migrated from spleen to peripheral lymphoid organs. Thus, in the very early phase of GHVD following Bu-Cy conditioning donor, DCs play an important role in the activation of donor T cells. Subsequently, donor naïve T-cells gain effector-memory phenotype and initiate GVHD.