Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in lymphocyte subsets during an acute GVH reaction were compared to STZ-induced PLN response in mice. The GVH reaction was induced locally by sc injection of parental C57Bl/6 [B6] spleen cells into (C57Bl/6 x DBA/2) F1 footpad [B6D2F1]. Early cell activation and time-related changes in T- and B-lymphocyte subsets were monitored during the onset of the GVH reaction by flow cytometry and immunophenotyping. Examination of cell size and chromatin decondensing for T- and B-cell subsets showed differences in activation profile during the early phase of the GVH reaction. The present study provides direct evidence for early in vivo activation of both CD4+ and CD8+ T-cells. Our data confirm the central role of T-cell activation in the induction of a GVH reaction and suggest that recirculatory host B-cells can play an important role in early GVH node enlargement. Overall, our comparative analysis supports the concept of polyclonal T-cell activation for both STZ-related and GVH-induced lymphoproliferation. Chemicals-induced lymphoproliferation leading to autoimmune reactions is a challenging issue. A number of drugs and chemicals have been tested in the PLNA assay for lymphoproliferative potential. We previously reported the activation and proliferation of T-cell subsets following STZ injection into murine footpads. The STZ-induced PLN enlargement and proliferation characteristics of T- and B-cell subsets were postulated to be similar to those of an acute allogeneic GVHR. In the present study, a cytometric analysis of T- and B-cell subsets in PLNs was performed during an acute allogeneic GVHR, for comparison purposes. Such a reaction results in a massive node enlargement five to ten times that seen after stimulation with conventional antigens. Acute GVHR is believed to be a direct consequence of the high frequency of alloreactive donor T-cells inducing a massive proliferation of B-cells, almost exclusively of host origin, in GVHR nodes. It is now widely accepted that donor T-cells activated as the result of exposure to foreign MHC antigens in the recipient, secrete various cytokines which assist the host B-cells and bypass the normal B-T cell cooperation. Induction of an acute GVHR, as in the parental B6--->recipient B6D2F1 model, requires the injection of CD4+ and CD8+ donor T-cells into an F1 recipient that differs from the parent at both MHC class I and II loci.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in the popliteal lymph node assay. II. Comparison with acute graft-vs-host reaction in H-2 incompatible F1 mouse hybrids. 136 74

UV-B irradiation (700 J/m2) of bone marrow cells (BMC) before transplantation into lethally irradiated (1050R) allogeneic rats prevents graft-versus-host disease (GVHD) and results in stable chimerism. This study examined whether UV-B modulation of BMT is useful in the subsequent induction of tolerance to small bowel transplant (SBT) and avoids the danger of GVHD, which remains the major obstacle to successful SBT. Lethally irradiated Lewis recipients of UV-B irradiated (700 J/m2) BMT (10(8) BMC admixed with 5 x 10(6) splenic leukocytes) either from ACI or Wistar-Furth (WF) rats developed stable chimerism without any evidence of GVHD for > 360 days. Lewis recipients of UV-B ACI BMC expressed 95 +/- 6% ACI lymphoid cells at 50 and 150 days after BMT using complement-dependent cytotoxicity assay. Unmodified Lewis recipients of orthotopic ACI SBT rejected their grafts and died in 7-9 days, whereas Lewis chimeras accepted permanently (> 200 days) bone marrow donor (ACI) SBT without any evidence of GVHD when the SBT was performed at 60 or 150 days after BMT. In contrast, when SBT was performed, only 30 days after induction of chimerism with UV-B ACI BMT, the recipients developed severe GVHD and died between 17 and 21 days. The Lewis chimeras rejected third part (WF) SBT acutely and died in 7-9 days, thus demonstrating the specificity of the induction of tolerance in this model. That this immunologic unresponsiveness is not restricted by the recipient-donor rat strain combination was shown by the permanent acceptance of WF SBT without GVHD by Lewis/WF chimeric recipients. Furthermore, the Lewis chimeras that were made diabetic with STZ 28 days after BMT permanently accepted (> 300 days) BM donor-type (WF) and recipient-type (Lewis) islet cells and became normoglycemic, thus indicating tolerance to both donor and recipient Ags. The diabetic Lewis chimeras that became normoglycemic permanently accepted (> 200 days) WF SBT without any evidence of GVHD after donor-type SBT 110 days after WF islet transplantation. The apparent lack of organ-specific unresponsiveness in this model confirmed our previous observation with combined islet and heart transplants. In vitro MLR studies showed that the chimeric animals were specifically unreactive to donor- and recipient-type alloantigens. Our results demonstrate that UV-B irradiation of BMT is a promising approach to the induction of tolerance to SBT.
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PMID:Prevention of graft-versus-host disease in rat small bowel transplantation by recipient pretreatment with UV-B-modulated bone marrow cells. 851 7

Induction of hematopoietic chimerism and subsequent donor-specific immune tolerance via bone marrow transplantation is an ideal approach for islet transplantation to treat type-1 diabetes. We examined the potential of mesenchymal stem cells (MSCs) in the induction of chimerism and islet allograft tolerance without the incidence of graft-versus-host disease (GVHD). Streptozotocin-diabetic rats received a conditioning regimen consisting of antilymphocyte serum and 5 Gy total body irradiation, followed by an intraportal co-infusion of allogeneic MSCs, bone marrow cells (BMCs) and islets. Although all the recipients rejected the islets initially, half of them developed stable mixed chimerism and donor-specific immune tolerance, shown by the engraftment of donor skin and second-set islet transplants and acute rejection of a third-party skin. The engraftment of the primary islet allografts with stable chimerism was achieved by the addition of a 2-week peritransplant administration of 15-deoxyspergualin (DSG). Without MSCs, none of the recipients treated with DSG developed chimerism or reversal of diabetes. GVHD was not observed in any of the recipients infused with MSCs (0/15), whereas it occurred in 4/11 recipients without MSCs. These results indicate a potential use of MSCs for induction of hematopoietic chimerism and subsequent immune tolerance in clinical islet transplantation.
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PMID:Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat. 1728 84