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Graft-versus-host Reaction (graft-versus-host + reaction)
Selected AbstractsNovel murine autoimmune-mediated liver disease model induced by graft-versus-host reaction and concanavalin AJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2001Rie Unno Abstract Background and Aims: We have previously reported that cluster of differentiation (CD)4+ T cells induced autoimmune liver diseases in mice with graft-versus-host reaction (GVHR) because of major histocompatibility complex (MHC) class II disparity. To analyze the progression of the autoimmune-related mechanism in the liver, concanavalin A (Con A) was injected in mice undergoing GVHR. The aim of this study is to clarify whether Con A deteriorates murine hepatic lesions induced by GVHR, and to elucidate the participation of the cytokines of liver-infiltrating CD4+ T cells. Methods: Mice (F1; B6.C-H-2bm12× B6) were intravenously injected with B6 T spleen cells. Concanavalin A (15 mg/kg) was administrated 5 days after cell transfer. We examined serum transaminase, antimitochondrial antibodies (AMA), antinuclear antibodies (ANA) and histological changes. Liver-infiltrating CD4+ T cells were sorted and their cytokine mRNA expression was examined by the use of reverse transcription,polymerase chain reaction (RT-PCR). Results: Graft-versus-host reaction + Con A mice revealed an elevated serum transaminase, elevated AMA and ANA titers, increased periportal cellular infiltration, piecemeal necrosis and bridging necrosis in the liver. In this group, interferon (IFN)-, mRNA expression was more elevated than it was in the GVHR mice. However, there was no difference in the expression of interleukin (IL)-10 mRNA between the two groups. Conclusion: The results suggest that Con A deteriorates the GVHR-induced hepatic lesions, and IFN-, and IL-10 of CD4+ T cells might be implicated in the progression of autoimmune-related hepatic lesions. This model might offer an aspect for the investigation of progressive mechanisms in T-cell- mediated hepatobiliary injury. [source] Adult thymus transplantation with allogeneic intra-bone marrow,bone marrow transplantation from same donor induces high thymopoiesis, mild graft-versus-host reaction and strong graft-versus-tumour effectsIMMUNOLOGY, Issue 4 2009Takashi Miyake Summary Although allogeneic bone marrow transplantation (BMT) plus donor lymphocyte infusion (DLI) is performed for solid tumours to enhance graft-versus-tumour (GVT) effects, a graft-versus-host reaction (GVHR) is also elicited. We carried out intra-bone marrow,bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor to supply alloreactive T cells continually. Normal mice treated with IBM-BMT + ATT survived for a long time with high donor-derived thymopoiesis and mild GVHR. The percentage of CD4+ FoxP3+ regulatory T cells in the spleen of the mice treated with IBM-BMT + ATT was lower than in normal B6 mice or mice treated with IBM-BMT alone, but higher than in mice treated with IBM-BMT + DLI; the mice treated with IBM-BMT + DLI showed severe GVHR. In tumour-bearing mice, tumour growth was more strongly inhibited by IBM-BMT + ATT than by IBM-BMT alone. Mice treated with IBM-BMT + a high dose of DLI also showed tumour regression comparable to that of mice treated with IBM-BMT + ATT but died early of GVHD. By contrast, mice treated with IBM-BMT + a low dose of DLI showed longer survival but less tumour regression than the mice treated with IBM-BMT + ATT. Histologically, significant numbers of CD8+ T cells were found to have infiltrated the tumour in the mice treated with IBM-BMT + ATT. The number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL)-positive apoptotic tumour cells also significantly increased in the mice treated with IBM-BMT + ATT. Allogeneic IBM-BMT + ATT thus can induce high thymopoiesis, preserving strong GVT effects without severe GVHR. [source] Popliteal lymph node assay: facts and perspectivesJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005Guillaume Ravel Abstract The popliteal lymph node assay (PLNA) derives from the hypothesis that some supposedly immunemediated adverse effects induced by certain pharmaceuticals involve a mechanism resembling a graft-versus-host reaction. The injection of many but not all of these compounds into the footpad of mice or rats produces an increase in the weight and/or cellularity of the popliteal lymph node in the treated limb (direct PLNA). Some of the compounds known to cause these adverse effects in humans, however, failed to induce a positive PLNA response, leading to refinements of the technique to include pretreatment with enzyme inducers, depletion of CD4+ T cells or additional endpoints such as histological examination, lymphocyte subset analysis and cytokine fingerprinting. Alternative approaches have been used to improve further the predictability of the assay. In the secondary PLNA, the test compound is injected twice in order to illicit a greater secondary response, thus suggesting a memory-specific T cell response. In the adoptive PLNA, popliteal lymph node cells from treated mice are injected into the footpad of naive mice; a marked response to a subsequent footpad challenge demonstrates the involvement of T cells. Finally, the reporter antigens TNP-Ficoll and TNP-ovalbumin are used to differentiate compounds that induce responses involving neo-antigen help or co-stimulatory signals (modified PLNA). The PLNA is increasingly considered as a tool for detection of the potential to induce both sensitization and autoimmune reactions. A major current limitation is validation. A small inter-laboratory validation study of the direct PLNA found consistent results. No such study has been performed using an alternative protocol. Other issues include selection of the optimal protocol for an improved prediction of sensitization vs autoimmunity, and the elimination of false-positive responses due to primary irritation. Finally, a better understanding of underlying mechanisms is essential to determine the most relevant endpoints. The confusion resulting from use of the PLNA to predict autoimmune-like reactions as well as sensitization should be clarified. Interestingly, most drugs that were positive in the direct PLNA are also known to cause drug hypersensitivity syndrome in treated patients. This observation is expected to open new avenues of research. Copyright © 2005 John Wiley & Sons, Ltd. [source] Novel murine autoimmune-mediated liver disease model induced by graft-versus-host reaction and concanavalin AJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2001Rie Unno Abstract Background and Aims: We have previously reported that cluster of differentiation (CD)4+ T cells induced autoimmune liver diseases in mice with graft-versus-host reaction (GVHR) because of major histocompatibility complex (MHC) class II disparity. To analyze the progression of the autoimmune-related mechanism in the liver, concanavalin A (Con A) was injected in mice undergoing GVHR. The aim of this study is to clarify whether Con A deteriorates murine hepatic lesions induced by GVHR, and to elucidate the participation of the cytokines of liver-infiltrating CD4+ T cells. Methods: Mice (F1; B6.C-H-2bm12× B6) were intravenously injected with B6 T spleen cells. Concanavalin A (15 mg/kg) was administrated 5 days after cell transfer. We examined serum transaminase, antimitochondrial antibodies (AMA), antinuclear antibodies (ANA) and histological changes. Liver-infiltrating CD4+ T cells were sorted and their cytokine mRNA expression was examined by the use of reverse transcription,polymerase chain reaction (RT-PCR). Results: Graft-versus-host reaction + Con A mice revealed an elevated serum transaminase, elevated AMA and ANA titers, increased periportal cellular infiltration, piecemeal necrosis and bridging necrosis in the liver. In this group, interferon (IFN)-, mRNA expression was more elevated than it was in the GVHR mice. However, there was no difference in the expression of interleukin (IL)-10 mRNA between the two groups. Conclusion: The results suggest that Con A deteriorates the GVHR-induced hepatic lesions, and IFN-, and IL-10 of CD4+ T cells might be implicated in the progression of autoimmune-related hepatic lesions. This model might offer an aspect for the investigation of progressive mechanisms in T-cell- mediated hepatobiliary injury. [source] Cytokine profile of liver-infiltrating CD4+ T cells separated from murine primary biliary cirrhosis-like hepatic lesions induced by graft-versus-host reactionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2000Shinichi Itoh Abstract Background and Methods: We have previously reported that CD4+ T cells induced primary biliary cirrhosis (PBC)-like hepatic lesions in mice with graft-versus-host reaction due to major histocompatibility complex class II disparity. To clarify the relationship between the cytokine profile produced by CD4+ T cells and the formation of hepatic lesions, we sorted CD4+ T cells from the liver by using flow cytometry and examined their cytokine mRNA expression at various times after GVHR induction. We also examined the associated changes in the serum levels of antimitochondrial antibodies (AMA). Results: Histologically, the infiltration of CD4+ T cells around the bile ducts was observed from day 5, and the lesions deteriorated gradually until day 14. On day 14, CD8+, B220+ and Mac-1+ cells, as well as CD4+ T cells were seen around the bile ducts. In the liver-infiltrating CD4+ T cells, the expression level of interferon-, (IFN-,) mRNA was observed to increase at an early phase (day 3), whereas that of interleukin (IL)-10 mRNA was elevated at a later phase (day 14). The elevation of IFN-, mRNA expression at an early phase before the appearance of non-suppurative destructive cholangitis suggests that IFN-, may be related to the pathogenesis of PBC in this model. Serum levels of AMA on day 14 were significantly higher than those on day 5. Interleukin-10 was considered to stimulate antibody production, to show an inhibitory effect upon the function of T helper 1 cells, and to inhibit fibrosis. Conclusions: Interferon-, may play an important role in the pathogenesis of this model. Moreover, delayed expression of IL-10 mRNA may control PBC-like hepatic lesions. [source] Erythema multiforme, Stevens,Johnson syndrome and toxic epidermal necrolysis: Frozen-section diagnosisTHE JOURNAL OF DERMATOLOGY, Issue 5 2010Hiroomi HOSAKA Abstract Stevens,Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may be fatal. Although classified by body surface area skin detachment, initial stages of both may present with erythema multiforme (EM)-like lesions. To diagnose and predict disease activity adequately as early as possible for patients revealing EM-like lesions, we performed frozen-section diagnosis. Thirty-five patients clinically diagnosed as EM, SJS or TEN were biopsied to diagnose and predict disease progression within the initial-visit day. Half of a histological section taken from a lesion was snap-frozen and immediately cryostat-sectioned, acetone-fixed and stained with hematoxylin,eosin. Specimens were examined with light microscopy for presence of epidermal necrosis. A section from unaffected sites was also examined for 11 patients. Specimens were examined with light microscopy for presence of graft-versus-host reaction (GVHR)-like findings: apoptotic keratinocytes and satellite cell necrosis. Epidermal necrosis was seen in nine patients. Initial diagnosis of the nine was one of overlap SJS-TEN, four of SJS and four of EM, and final diagnosis of those was one of TEN, one of overlap SJS,TEN, four of SJS and three of EM. Dissociation between initial and final diagnosis was seen in three cases. GVHR-like findings in the epidermis were observed in two patients finally diagnosed as overlap SJS,TEN and TEN. Frozen sections are useful not only to make a diagnosis of erythema multiforme but to assess a potential to exhibit more aggressive clinical behaviors (SJS or TEN). [source] | ||||||||||