No abstract available.
Adult ; Chronic Disease ; Graft vs Host Disease/*pathology ; Humans ; Liver/*pathology ; Male

Recently there are increasing evidence of the existence of an immune-mediated endothelial-cell injury in the acute graft-versus-host disease (aGVHD). Endothelial cells are an important target in the process of GVHD immune attacking, and vascular end thelial injure is an early event of tissue injury caused by aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Biomarkers for endothelial damage were consisted with endothelia injury, which may be considered a valuable marker to confirm GVHD diagnosis. The endothelial cell phenotype differs between organs, which results in organ-dependent differences for the involved organs when GVHD occurring. Although the endothelial cells play an impartant tole in process of aGVHD occurence, a further research to better characterize its role in allo-HSCT is needed. This review focusses on the research progress of aGVHD after allo-HSCT and endothelial-cell injury, as well as is markers so as to provide corresponding strategies and targets for the prevent and treatment of a GVHD.
Biomarkers ; Endothelial Cells ; pathology ; Graft vs Host Disease ; physiopathology ; Hematopoietic Stem Cell Transplantation ; Humans

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method for the treating of malignant diseases of hematopoietic system or non-malignant proliferative diseases, but the occurrence of graft-versus-host disease (GVHD) limits the success rate of hematopoietic stem cell transplantation. Moreover, chronic graft-versus-host disease (cGVHD) is the main factor affecting the long-term survival rate and life quality of recipient after hematopoietic stem cell transplantation. In this article, the latest research progress of the pathogenesis of cGVHD and related problems are reviewed from the thymus, cytokines, T lymphocyte subsets, B lymphocytes and its secreted antibody.
Chronic Disease ; Graft vs Host Disease ; immunology ; pathology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Transplantation, Homologous

To overcome poor graft function after allogeneic bone marrow transplantation (BMT), the use of peripheral blood stem cells (PBSC) instead of bone marrow is gaining more popularity because of its advantages. There may, however, be an increased risk of graft-versus-host-disease (GVHD) because of the large number of lymphocytes present in a leukapheresis product. An 18-year-old man with severe aplastic anemia underwent an allogeneic BMT using his HLA-identical sister. After initial excellent graft take for 8 months, his blood counts gradually decreased to 2.8 x 10(9)/L of white cells and 28 x 10(9)/L of platelets with marrow cellularity of < 10%. After allogeneic granulocyte-colony stimulating factor mobilized PBSC rescue, the patient's blood counts recovered satisfactorily. Around 1 year after the boost, he developed chronic GVHD that responded to prednisolone and cyclosporin A. He is now well on low-dose steroids at day +1055 after PBSC rescue. The present case is the first experience of a long-term follow-up who underwent allogeneic PBSC rescue in Korea.
Adolescence ; Anemia, Aplastic/therapy ; Anemia, Aplastic/blood ; Bone Marrow Transplantation/adverse effects* ; Chronic Disease ; Cyclosporine/therapeutic use ; Female ; Graft vs Host Disease/pathology ; Graft vs Host Disease/etiology* ; Graft vs Host Disease/drug therapy ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Human ; Male ; Prednisolone/therapeutic use

Graft-versus-host disease (GVHD) is a life threatening complication that may occur following allogenic bone marrow transplantation (BMT) in the patients with aplastic anemia, leukemia or genetic immunodeficiency. It has been known that GVHD occurs approximately 70% of recipients of BMT in western countries but no definite incidence has been reported in Korea. In our St. Mary's Hospital, GVHD occurs in about 30% of BMT recipients. Histopathologically the acute phase skin shows diffuse lymphocytic infiltrates in the upper dermis with extensive exocytosis. Scattered throughout the epidermis are many degenerated keratinocytes, which are often associated with one or more satellite lymphocytes (satellite cell necrosis). In the chronic phase, acanthosis, eosinophilic keratinocytes resembling colloid bodies and mononuclear cell infiltrates in the upper dermis are noted. We reviewed 5 cases of acute GVHD and 6 cases of chronic GVHD. All patients received allogenic BMT from Jan. 1, 1992 to July 1, 1993. Ten patients were male and one was female. The mean age was 34 (20-70). The pathologic diagnosis was 3 cases of CML, 2 of ALL, 2 of AML (FAB M2), 2 of aplastic anemia, 1 of CLL and 1 of AML (FAB M5). The interval from BMT to GVHD varied from 14 days to 4 years (median 220 days). The skin and GI tract were involved in all eleven cases. Ten cases were histologically proven by skin biopsies, and two cases by salivary gland and colonic biopsies, respectively. The histological findings of the skin, salivary gland and colonic biopsieds were described. Immunohistochemical stain of the skin was done using CD4, CD8, HLA DR and Leu 7 antibodies.
Adult ; Aged ; Antigens, CD4/analysis ; Antigens, CD8/analysis ; Biopsy ; Female ; Graft vs Host Disease/immunology/*pathology ; HLA-DR Antigens/analysis ; Human ; Immunohistochemistry ; Male ; Middle Age

To observe the graft-versus-host disease (GVHD) in rat-to-mouse model of bone marrow transplantation to build a GVHD model, BALB/c mice were conditioned with 8.5 Gy lethal total body irradiation and divided into two groups. One group of mice was infused with 4 x 10(7) bone marrow cells (BMC) from SD rats. The other group of mice was infused with 4 x 10(7) bone marrow cell and 2 x 10(7) spleen cells from SD rats. GVHD in mice of two groups were observed for 60 days. The results showed that mice in the group infused with only BMC mostly (80%) survived more than 60 days, but in the other group infused with mixed BMC and spleen cells, all mice died within 14 days and showed GVHD with pathologic evidence. In conclusion, to induce GVHD in rat-to-mouse bone marrow transplantation needs additional rat spleen cells.
Animals ; Bone Marrow Transplantation ; immunology ; mortality ; Graft vs Host Disease ; etiology ; pathology ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Survival Rate ; Transplantation, Heterologous ; immunology

OBJECTIVETo explore the role of Th17 cells in early onset of acute graft-versus-host disease (aGVHD) and its mechanism.

METHODSMice aGVHD model was established by irradiated BABL/c mice inoculated with mixed suspension of C57BL/6 bone marrow cells and splenocytes. The mice were divided into 4 groups: (1) normal control, (2) irradiated group, (3) allo-BMT + DMSO group, (4) allo-BMT + halofuginone (HF) group. HF was given intraperitoneally at 5 µg per mouse from -1 d to +10 d after allogeneic bone marrow transplantation(allo-BMT).Mice aGVHD symptoms and survival were observed. Th1/Th17 cells ratio was evaluated by flow cytometry.

RESULTSAll the experimental groups (3) and (4) developed aGVHD after transplantation. More severe aGVHD was observed in group (4) than in group (3). HF prevented cutaneous aGVHD in all the mice, but augmented hepatic and small intestine GVHD. The percentage of Th17 cells and the ratio of Th1/Th17 were significantly higher while the percentage of Th1 cells was significantly lower in group (4) at day +6 (P < 0.05).

CONCLUSIONEarly blockage of Th17 cell results in increase of Th1 cell percentage, which exacerbates aGVHD.

Animals ; Bone Marrow Transplantation ; Female ; Graft vs Host Disease ; etiology ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Th1 Cells ; cytology ; Th17 Cells ; cytology ; Transplantation, Homologous

The objective of this study was to analyze the relationship between some chemokines and the pathogenesis of GVHD and to find some biomarkers with diagnostic significance through observing and comparing the changes of some chemokine levels in samples from patients with or without aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 26 plasma samples were obtained from 26 patients undergoing allo-HSCT at various time points after transplantation, of which 13 samples from patients with aGVHD were served as investigating group and 13 samples from patients without GVHD after Allo-HSCT were used as control group. The patient characteristics between the two groups were compared, the levels of 40 chemokines in these samples were detected by ELISA, the changes of chemokine levels in samples of 2 groups were analyzed by means of significance analysis microarray (SAM), clustering method and c-test. The results showed that there were significant differences in levels of 6 chemokines including HCC-1, MIF, IP-10, ITAC, TARC and NAP-2 between 2 groups, in which the level of MIF in plasma samples after HSCT was the highest, the difference of TARC level between 2 groups was over 10-fold. It is concluded that the level changes of chemokines mentioned above can be used as a indicator of GVHD presence, but their pathogenetic role in occurrence of aGVHD remains to be determined.
Adolescent ; Adult ; Chemokines ; blood ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; blood ; pathology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Transplantation, Homologous ; Young Adult

This study was aimed to explore the influence of excessive complement activation on the pathological process of acute graft-versus-host disease (aGVHD) in mice. A murine model with aGVHD was established by injecting cell mixture containing splenocytes and bone marrow cells at 2:1 ratio from donor C57BL/6(H-2K(b)) mice into recipient BALB/c (H-2K(d)) mice within 4-6 hours after 8 Gy (60)Co γ-ray total body irradiation. The mice received syngeneic bone marrow transplantation were used as control group. After transplantation, the mice were monitored daily for body weight and mortality. At day 14, all mice were sacrificed and each liver was freshly dissociated for histological analysis. The hepatic mRNA abundance for complement components C3a and C5a as well as receptors for these two anaphylatoxin were tested by real-time quantitative PCR method. And the levels of C3a and C5a production in liver were detected by ELISA. The deposition of complement C3 in liver was determined by immunofluorescence staining using frozen section. The results indicated that as compared with syngeneic bone-marrow transplantation control group, experimental animals underwent aGVHD characterized by weight loss, depilation, diarrhea and lassitude. Interestingly, the hepatic mRNA expression for complement anaphylatoxin family member C3a and C5a as well as their receptors C3aR and C5aR1 in mice with aGVHD were significantly up-regulated in comparison with control group (p < 0.05). Consistently, the content of C3a and C5a in liver increased markedly in mice with aGVHD (p < 0.01). For animals ongoing aGVHD, complement component C3 depositions were observed in hepatic portal areas, around which massive inflammatory cell infiltration was also observed. It is concluded that in aGVHD animals, excessive complement activation occurs, and the activated complement components participate in pathological process of the aGVHD.
Animals ; Bone Marrow Transplantation ; Complement Activation ; Female ; Graft vs Host Disease ; immunology ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL

This study was purposed to detect the expression level of human endothelial cell tissue factor (hECTF) and concentration of IL-2, and to investigate the alterations of hECTF and IL-2 after using immunosuppressive agent (cyclosporin, CsA) and explore the significance of endothelial cell (EC) lesion and abnormal expression of tissue factor (TF) in GVHD. Human endothelial cells and allogeneic lymphocytes were mixed and cultured as well as were cocultured with CsA for 4-6 hours in vitro, then the expression level of hECTF was detected by flow cytometry and RT-PCR, the concentration of IL-2 in supernatant was assayed by ELISA. The experiment was divided into 4 groups: 1st group--non-mixed-cultured group (negative control group), 2nd group - mixed-cultured group (positive control group), 3rd group - mixed-cocultured group with 1 µg/ml CsA and 4th group--mixed-cocultured group with 2 µg/ml CsA. The results showed that as compared with non-mixed-cultured group (negative control group), the expression level of hECTF and concentration of IL-2 in another 3 groups significantly increased (p<0.01), while as compared with positive control group, the expression level of hECTF and concentration of IL-2 in cocultured groups with CsA both decreased (p<0.01). It is concluded that the lesion of EC and abnormal expression of TF play a crucial role in GVHD, among which the high expression of TF after being stimulated by donor's lymphocytes may be the key step for occurrence and progression of GVHD.
Cells, Cultured ; Coculture Techniques ; Cyclosporine ; pharmacology ; Endothelial Cells ; metabolism ; Graft vs Host Disease ; metabolism ; pathology ; Humans ; Interleukin-2 ; metabolism ; Lymphocytes ; cytology ; Thromboplastin ; metabolism