Cytokine Profiles in Various Graft-Versus-Host Disease Target Organs following Hematopoietic Stem Cell Transplantation

Cell Transplantation

Article

Teh-Ying Chou¹  Hsiu-Yu Lai²  Oscar Kuang-Sheng Lee³  Cheng-Hwai Tzeng⁴ 

[1] Department of Pathology, Taipei Veterans General Hospital, Taiwan;Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan;Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan;Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan;Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan;Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taiwan;Section of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taiwan;

关键词: Graft-versus-host disease (GvHD);    Bone marrow transplantation (BMT);    T-helper (Th) cell;    Cytotoxic T (Tc) cell;   

DOI  :  10.3727/096368912X653110

 received in 2011-04-10, accepted in 2011-11-15,  发布年份 2012

来源: Sage Journals

【 摘 要 】

Previous studies using genetic-deficient murine models suggest that different T-helper subsets may contribute to different types of tissue damages in graft-versus-host disease (GvHD). However, there is limited information available on the distribution of T-helper cytokines in the various GvHD target tissues. In the current study, an acute GvHD murine model was set up to directly assess the in situ cytokine profiles in various GvHD tissue lesions; in addition, we also studied GvHD tissues from patients who had undergone bone marrow transplantation procedures. We observed that interferon-γ (IFN-γ was dominant in murine liver and gastrointestinal tissue lesions, whereas IFN-γ and interleukin 17 (IL-17) were abundant in murine skin lesions. Furthermore, in human GvHD tissues, interleukin 4 (IL-4) and IFN-γ were predominant in liver lesions and colon lesions, respectively, while no specific cytokine was prevalent in human GvHD skin lesions. In addition, a low ratio of CD4+ T helper (Th) versus CD8+ T cytotoxic (Tc) cells in human GvHD tissue lesions, especially in the liver, was detected, and this contrasts with the situation in murine GvHD tissues where CD4+ Th cells were predominant. Dual staining for CD markers and cytokine expression showed that IFN-γ-secreting T cells were enriched in all murine GvHD target tissue lesions, and Tc1 and Tc2 cells were predominant in human GvHD colon and liver sections, respectively. However, IFN-γ+ Th1, IL-17+ Th17, IFN-γ+ Tc1, and IL-17+ Tc17 cells were slightly more frequent in human skin lesions compared to IL-4+ Th2 and IL-4+ Tc2 cells. To sum up, these results suggest that differences in cytokine imbalances may significantly contribute to tissue-specific pathogenesis in GvHD target organs, and CD8+ Tc cells may play an important role in human GvHD induction.

【 授权许可】

Unknown   
© 2012 Cognizant Comm. Corp.

【 图 表 】

Figure 2.

Figure 1.