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)

Serum complement (C) and C components were examined during a systemic graft versus host (GVH) reaction in the rat. In our series of experiments (Lewis times Brown Norway) F-1 hybrid rats (60-80g) were given 200 times 10-6 or 400 times 10-6 Lewis spleen cells intravenously. Clinical GVH disease appeared 5-7 days after cell injection. Five of six rats in the experimental groups had a fall in levels of serum C2 (20-76%) and C4 (75-98%). Only one of six rats in the control group had a significant fall in C components. In a subsequent experiment (Fisher 344 times Brown Norway) F-1hybrid rats (60g) were given 400 times 10-6 Fischer 344 spleen cells or 200 times 10-6 Fischer 344 Ficoll-Hypaque separated spleen lymphocytes. Clincal GVH disease in this instance appeared on day 10. As in the previous experiments C2 and C4 fell markedly, 20-60% and 60-8-%, respectively, from baseline titers. The control groups did not have a significant fall in C2 or C4. Further examination showed reduction in C3, C5, C6,AND C8 suggesting a sequential activation of the C system via the classical pathway. We have postulated that the cells undergoing blast transformation may be activating the C system through membrane changes during the GVH reaction. Furthermore, the deficiency of C AND C components during GVH disease may contribute to the increased susceptibility of the host to infection and sepsis.
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PMID:Complement in graft versus host disease: IL Depletion of complement components during a systemic graft versus host reaction in the rat (38499). 23 66

Graft-versus-host disease (GVHD) remains a major complication of allogeneic bone marrow (BM) transplantation. Techniques that effectively purge BM of mature T lymphocytes should reduce the incidence of GVHD and improve survival. We have developed a simplified, two-flow rate, fixed rotor speed counterflow centrifugation-elutriation (CCE) procedure that reproducibly depletes 99% of lymphocytes from Ficoll-Hypaque(F/H)-separated BM or BM buffy-coat. Two predetermined flow rates (24 and 28 ml/min) were used to purge small and intermediate-to-large lymphocytes, respectively, whereas faster sedimenting cells were recovered at the termination of the run. Lymphocyte depletion was substantiated by pan-T monoclonal antibody analysis as well as by complete loss of responsiveness to alloantigens and mitogens. Despite the lack of mature T cells, the depleted marrow fraction retained lymphoid colony-forming ability. Lymphocyte-purged marrow was obtained in high yield (72%), and retained high viability (greater than 97%) and hematopoietic colony-forming ability (greater than 99%). The ratio of total myeloid/erythroid colony-forming cells to T lymphocytes was 73-fold higher in the lymphocyte-depleted fraction than in unseparated BM. We concluded that a two-step CCE procedure can be used to rapidly deplete lymphocytes from both F/H-separated and buffy-coat BM inocula without altering hematopoietic capacity as measured by the in vitro clonogenic assays. It may be possible to adapt this procedure to the separation of the large number of marrow cells required for human BM transplantation.
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PMID:Development of a simplified counterflow centrifugation elutriation procedure for depletion of lymphocytes from human bone marrow. 293 79

We studied optimal conditions for ex vivo elimination of mature T cells from human bone marrow by T101 immunotoxin (T101-IT) with criteria applicable to graft-versus-host disease (GVHD) prophylaxis prior to allogeneic marrow transplantation. T101-IT consisted of T101 anti-CD5 monoclonal antibody conjugated to purified ricin A-chain toxin. Marrow mononuclear cells isolated by Ficoll-Hypaque or by fractionation with soybean lectin (SBA- cells) were incubated with T101-IT at 37 degrees C with or without ammonium chloride and/or verapamil as potential enhancers of immunotoxin potency. As controls, competitive inhibition studies with unconjugated T101 or irrelevant IgG2a antibody were carried out. Residual T cells were quantified by limiting dilution in phytohemagglutinin (PHA)-interleukin 2 (IL-2) feeder-cell-containing microcultures and hematopoietic progenitors by CFU-GM assay. We demonstrated that T101-IT in the range of 1-100 nM does not affect early total cell viability; that its delayed cytotoxicity is T-cell-specific, greatly enhanced by ammonium chloride, and moderately by verapamil--which also is not synergistic with ammonium chloride; and that 10 nM X 3 fractionated doses (i.e., added at 0, 1.5, and 3 hr of incubation) in the presence of 10 mM ammonium chloride for 4 hr at pH 7.8 consistently induces 2 log T cell depletion. In addition, if the same T101-IT treatment is preceded by fractionation with soybean lectin (i.e., T101-IT treatment of SBA- marrow cells), 3 log T cell depletion is accomplished. We conclude that T101-IT is highly effective in eliminating T cells from donor grafts. However, data presented here indicate that T101-IT should be associated with additional methods, such as soybean lectin fractionation, to ensure more effective ex vivo T cell depletion and acute GVHD prevention.
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PMID:Specific ex-vivo depletion of human bone marrow T lymphocytes by an anti-pan-T cell (CD5) ricin A-chain immunotoxin. 310 75

Alloantigen-specific hyporesponsiveness can be induced in alloreactive T cells contained within the whole peripheral blood mononuclear cell (PBMC) population by stimulating these responder cells ex vivo with HLA-mismatched stimulator PBMC as the antigen presenting cell (APC) source, in the presence of a CD28 costimulation blocking agent. As a result of this approach, specific alloreactivity is markedly decreased (by 1-2 logs), but third-party alloresponses and in vitro responses relying on the activation of pathogen- and tumor-associated antigen T-cell functional activities are not globally impinged upon (Guinan et al. N Engl J Med 340(22):1704-1714, 1999, Davies et al. Transplantation 86(6):854-864, 2008, Davies et al. Cell Transplant 21(9):2047-61, 2012). This method has been used clinically to alloanergize bone marrow and PBMC allografts, creating ex vivo cell therapies for adoptive transfer to blood cancer patients at high risk of disease relapse whose best option was to receive haploidentical hematopoietic cell transplants. These early phase trials consisting of, or containing, alloanergized T-cell infusions show promise in reducing graft-versus-host disease (GvHD), providing more rapid immune reconstitution, and decreasing severe post-transplant infectious complications and disease relapse. Herein, we describe this straightforward technique for generating alloanergized PBMC as it is performed in the research lab setting using belatacept for CD28-mediated costimulatory blockade (CSB) and PBMC isolated by Ficoll Hypaque gradient centrifugation as responders and APC. We also describe methods for evaluating subsequent alloproliferation to first and third party stimulation as well as assessment of cell division, pathogen-specific immunity, or allosuppression. The technique has successfully been transferred to collaborating labs, largely owing to the flexibility of using fresh or frozen PBMC, the lack of a requirement for specially isolated APC populations, and the ability to scale up or scale down the cell numbers that are to be anergized.
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PMID:Alloanergization Method for Inducing Allospecific Hyporesponsiveness in PBMC Exposed to Allostimulation In Vitro in the Context of Costimulatory Molecule Blockade. 3064 68