Evidence that the elevation of soluble MHC class I antigens in the serum precedes the onset of graft-versus-host disease and is correlated with the severity of the disease in rats

Kimura, Takefumi; Enosawa, Shin; Kamada, Nanao; Kobayashi, Eiji; Toyama, Nobuyuki; Doy, Mikio; Matsuzaki, Yasushi; Tanaka, Naomi; Osuga, Toshiaki

doi:10.1016/0966-3274(95)80015-8

Cited by 6 publications

(2 citation statements)

References 23 publications

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“…Especially the strains Brown-Norway (BN) and Lewis (LEW) are widely used for fully MHC mismatched alloHCT (Santos and Owens, 1966; Clancy et al, 1976; Pakkala et al, 2001; Okayama et al, 2004; Zhu et al, 2011; Lin et al, 2012). Also HCT between haploidentical parental and filial generations, e.g., transplantation of LEW or BN bone marrow into F 1 (BN × LEW) recipients, has been modeled in the rat (Clancy et al, 1983; Kimura et al, 1995; Ohajekwe et al, 1995; Peszkowski et al, 1996; Vaidya et al, 1996; Goral et al, 1998; Kobayashi et al, 1998; Sasatomi et al, 2005; Wolff et al, 2006; Kitazawa et al, 2012). In a number of these models, engraftment, reconstitution, chimerism, cell trafficking, and tolerance toward donor cells has been studied (Clancy et al, 1983; Oaks and Cramer, 1985; Ohajekwe et al, 1995; Engh et al, 2001; Foster et al, 2001; Okayama et al, 2004; Itakura et al, 2007; Klimczak et al, 2007; Nestvold et al, 2008; Zhou et al, 2008; Zhu et al, 2011; Zinöcker et al, 2011a;Lin et al, 2012).…”

Section: Hematopoietic Cell Transplantation In Humans and Animalsmentioning

confidence: 99%

Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

Zinöcker¹,

Dressel²,

Wang³

et al. 2012

Front. Immun.

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Allogeneic hematopoietic cell transplantation (alloHCT) extends the lives of thousands of patients who would otherwise succumb to hematopoietic malignancies such as leukemias and lymphomas, aplastic anemia, and disorders of the immune system. In alloHCT, different immune cell types mediate beneficial graft-versus-tumor (GvT) effects, regulate detrimental graft-versus-host disease (GvHD), and are required for protection against infections. Today, the “good” (GvT effector cells and memory cells conferring protection) cannot be easily separated from the “bad” (GvHD-causing cells), and alloHCT remains a hazardous medical modality. The transplantation of hematopoietic stem cells into an immunosuppressed patient creates a delicate environment for the reconstitution of donor blood and immune cells in co-existence with host cells. Immunological reconstitution determines to a large extent the immune status of the allo-transplanted host against infections and the recurrence of cancer, and is critical for long-term protection and survival after clinical alloHCT. Animal models continue to be extremely valuable experimental tools that widen our understanding of, for example, the dynamics of post-transplant hematopoiesis and the complexity of immune reconstitution with multiple ways of interaction between host and donor cells. In this review, we discuss the rat as an experimental model of HCT between allogeneic individuals. We summarize our findings on lymphocyte reconstitution in transplanted rats and illustrate the disease pathology of this particular model. We also introduce the rat skin explant assay, a feasible alternative to in vivo transplantation studies. The skin explant assay can be used to elucidate the biology of graft-versus-host reactions, which are known to have a major impact on immune reconstitution, and to perform genome-wide gene expression studies using controlled combinations of minor and major histocompatibility between the donor and the recipient.

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Section: Hematopoietic Cell Transplantation In Humans and Animalsmentioning

confidence: 99%

Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

Zinöcker¹,

Dressel²,

Wang³

et al. 2012

Front. Immun.

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“…Viable splenocytes were separated using a slightly modified technique described by Kimura et al [26]. Briefly, spleens from Lewis rats were minced and passed through 200-mesh stainless steel filters with 20 volumes of ice-cold RPMI-1640.…”

Section: Methodsmentioning

confidence: 99%

Correlation of Chimerism with Acute Graft-versus-Host Disease in Rats following Liver Transplantation

Chen

Bai

et al. 2011

International Journal of Hepatology

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The accurate diagnosis of acute graft-versus-host disease following liver transplantation (LTx-aGVHD) has been hampered. Chimerism appears in the majority of recipients after LT and its significance in the diagnosis of LTx-aGVHD has not been clearly established. To demonstrate the significance of chimerism on the diagnosis of LTx-aGVHD, we compared the change of chimerism in syngeneic LT recipients, semiallogeneic LT recipients, and LTx-aGVHD induced recipients. Chimerism in PBMCs following sex-mismatched LT was identified by real-time PCR based on a rat Y-chromosome-specific primer. All recipients in semiallogeneic group grew in a normal pattern. However, when 4 × 108 donor splenocytes were transferred simultaneously during LT, the morbidity of lethal aGVHD was 100%. The chimerism appeared slightly higher in the semiallogeneic group than in the syngeneic LT group, but the difference was not significant. However, when the recipients developed lethal aGVHD after LT, chimerism in the PBMCs increased progressively, and even at an early time, a significant increase in chimerism was observed. In conclusion, high level chimerism correlated well with LTx-aGVHD, and detection of chimerism soon after transplantation may be of value in the diagnosis of LTx-aGVHD prior to the onset of symptoms.

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Timing of lymphocyte transfusion and portal clamping for the development of lethal graft-versus-host disease in the rat

Kobayashi¹,

Enosawa²,

Fujimura

et al. 1998

Surg Today

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The effects of surgical intervention on the incidence and augmentation of graft-versus-host disease (GVHD) were studied in the rat. To elicit GVHD, splenocytes from parental LEW rats at a dose of 4 x 10(8) or 1.5 x 10(8) cells/350g body weight were injected via the tail vein into (LEW x BN)F1 rats. The injection of 4 x 10(8) of LEW rat splenocytes induced lethal GVHD in all nontreated F1 rats, while 1.5 x 10(8) of LEW splenocytes did not induce any signs of GVHD. However, when the F1 rats had received the same dose of parental LEW lymphocytes in combination with portal clamping, 14 recipients out of the 15 rats (93%) suffered GVHD and 10 rats (67%) died from GVHD. Interestingly, portal clamping 7 days after the injection enhanced the incidence of GVHD, whereas no GVHD was observed in the intervention group either 3 or 7 days prior to the cell transfusion. When 1.5 x 10(8) of allogeneic lymphocytes were injected intravenously together with 0.1-1.0 mg/kg of endotoxin instead of portal clamping, the injection led the early death by GVHD, while the injection of methylpredonisolone did not enhance GVHD. These results thus indicate that either simultaneous or delayed surgical intervention has the potential to trigger a dormant state in transferred alloreactive lymphocytes.

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Evidence that the elevation of soluble MHC class I antigens in the serum precedes the onset of graft-versus-host disease and is correlated with the severity of the disease in rats

Cited by 6 publications

References 23 publications

Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

Correlation of Chimerism with Acute Graft-versus-Host Disease in Rats following Liver Transplantation

Timing of lymphocyte transfusion and portal clamping for the development of lethal graft-versus-host disease in the rat

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