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

Hemopoietic grafts following 1,200 R of total body irradiation were carried out between canine littermates homozygous or heterozygous for lymphocyte defined (LD) antigens of the major histocompatibility complex (MHC). In all but five of the 25 pairs studied, LD homozygous dogs were also homozygous for serologically defined (SD) antigens of the MHC. Results of transplants were compared with previous results obtained in littermate pairs matched or mismatched for the MHC. Two groups of recipients were studied. Of 14 LD homozygous recipients in group 1 given grafts from LD heterozygous donors, 12 died between 8 and 193 days and two survived more than 238 and 627 days. The most frequent cause of death was graft-versus-host disease (GVHD). Survival was significantly shorter (P less than 0.005) than that of dogs given grafts from matched littermates and not different (P congruent to 0.5) from that of dogs given grafts from mismatched littermates. Survival of 11 LD heterozygous recipients in group 2 given grafts from LD homozygous donors was not different from that of dogs in group 1 (P congruent to 0.5). The results indicate that the LD loci detected by mixed leukocyte culture are not the principal determinants within the MHC that are responsible for GVHD.
 ...
PMID:Marrow grafts between canine litter-mates homozygous or heterozygous for lymphocyte-defined histocompatibility antigens. 0 64

Pre-sensitization was investigated in the dog marrow transplant model with donor and recipient mismatching at the canine major histocompatibility complex (MHC). Various prophylactic immunosuppressive regimes were used and it was concluded from these regimes that sensitization to histocompatibility antigens could be abrogated by a combination of procarbazine and antithymocyte serum (ATS) together, before total body irradiation. Subsequent work in humans showed that rejection of a bone marrow graft can be successfully treated by using the procarbazine-antithymocyte clobulin regime and a second transplant. Based upon animal studies, attempts were made to prevent graft-versus-host disease in humans by the use of methotrexate following grafting. Despite matching at the MHC and the use of methotrexate some recipients developed graft-versus-host disease with a fatal outcome. Further work using ATS in the immediate pre- and post-grafting period was inconclusive. Accordingly ATS was used in animals once graft-versus-host disease became manifest with drmatic improvement in clinical status. As a result it was decided to treat all patients who developed graft-versus-host disease with antithymocyte globulin (ATG). Under ATG therpy twelve out of nineteen patients showed complete resolution, and five showed improvement. Six patients became long term survivors. Of the remaining 13, 11 died on interstitial pneumonitis, and two of fungal and bacterial infections. ATG in estblished graft-versus-host disease appears capable of modigying an otherwise fatal disease in a therpeutically beneficial manner.
 ...
PMID:Use of antithymocyte serum in clinical and experimental marrow transplantation. 1 56

Bone marrow transplantation can be considered in any disease state resulting in the malfunction or absence of part or all bone marrow elements. Diseases such as aplastic anemia, leukemia, and immunodeficiency disease are being treated with bone marrow transplantation. As with any organ transplant, graft rejection is a possibility. In bone marrow transplantation, there is the additional, unique problem of graft versus host disease. In order to prevent or minimize graft rejection, the immunocompetence of the recipient and the degree of disparity between donor and recipient at the major histocompatibility complex (MHC) loci are considered. The results of bone marrow transplantation are variable, and the mortality rate is still relatively high. However, progress is being made, and in many instances, normal bone marrow function can be restored in patients with whom other treatment has failed.
 ...
PMID:Bone marrow transplantation. 3 23

It is demonstrated that, under experimental conditions resembling those used for bone marrow grafting in man, disparity for minor histocompatibility antigens alone (i.e., antigens coded for by genes not included in the major histocompatibility complex) is in fact sufficient for the induction of severe lethal graft-versus-host disease in adult (DBA/2 X B10.D2)F1 recipients of normal B10.D2 myeloid and lymphoid cells.
 ...
PMID:Non-H-2 antigens can induce high GVH mortality in adult recipients of normal cells. 3 44

These studies consider the generation of cytotoxic T lymphocytes (CTL) from precursors (CTLP) present in rat thoracic duct lymphocytes after stimulation with strong alloantigens. Also, they explore the relationship between CTLP and "initiator" (I) lymphocytes responsible for specific GVH and MLI reactions. Positively selected TDL populations prepared in bulk MLI cultures show enriched GVH and MLI reactivity for the selecting major histocompatibility complex (MHC) haplotype, but no cytotoxic activity, raising the possibility that I and CTLP may belong to different subpopulations, and the latter failed to differentiate or to survive under these culture conditions. Restimulation of these cells in Marbrook culture vessels with the original priming haplotype under conditions suitable for generating killer cells in vitro resulted in greatly increased specific CTL activity with accelerated kinetics soon after priming and normal kinetics later. These findings indicate that "memory" killer cells can be generated in a previously stimulated lymphocyte population that had no overt cytotoxic activity. Restimulation with third party haplotypes failed to give CTL activity either to specific or to third party targets. Negatively selected TDL populations prepared by "filtration" through x-irradiated F1 rats, depleted of specific GVH and MLI responses, were also depleted of the ability to generate CTL in Marbrook cultures stimulated with the selecting haplotype. Stimulation with third party haplotypes, or with both third party and specific haplotypes together, gave CTL effective only against the third party target.
 ...
PMID:Specific selection of cytotoxic effector cells: the generation of cytotoxic T cells in rat thoracic duct lymphocyte populations positively or negatively selected for reactivity to specific strong histocompatibility alloantigens. 5 40

Graft-vs.-host reaction (GVHR) induced in non-irradiated F1 mice with DBA/2J parental spleen and lymph node (LN) cells usually does not lead to acute GVH disease (GVHD). This contrasts with the GVHR induced in other parent-F1 combinations involving both major histocompatibility complex (MHC) class I and class II differences between donor and host. Most signs of acute GVHD in non-irradiated F1 mice relate to immunodeficiency following destruction of the lymphohemopoietic system of the host, which leads to wasting and death due to infections. This sequence of events is prevented when donor lymphoid cells, originating from grafted stem cells, repopulate the destroyed lymphohemopoietic system of the host. To examine whether a "silent" repopulation of the F1 host by donor stem cells might underly the absence of clinical signs of acute GVHD when GVHR is induced with DBA/2J lymphoid cells, GVHR was induced with LN cells, which do not contain stem cells. Indeed, GVHR induced in (C57BL/10 x DBA/2J)F1 (BDF1) mice with 80 x 10(6) DBA/2J LN cells led to acute GVHD. Signs of acute GVHD such as wasting and death did not occur when donor stem cells, from an inoculum of DBA/2J spleen and LN cells, were allowed to repopulate the lymphohemopoietic system of the host. The effect of donor stem cells on clinical signs of acute GVHD was more apparent when (B10.D2 x DBA/2J)F1, instead of DBA/2J, lymphoid cells were used to induce GVHR. The detection of alloreactive anti-host cytotoxic T lymphocyte (CTL) activity during acute GVHD induced with DBA/2J donor lymphoid cells supports the hypothesis that such CTL contribute to the destruction of the host immune system in acute GVHD.
 ...
PMID:Protection from lethal graft-vs.-host disease by donor stem cell repopulation. 134 16

To assess the hypothesis that the human immunodeficiency virus (HIV) might mimic major histocompatibility complex (MHC) allodeterminants and interact with T-cell receptors (TCRs) of alloreactive T-cells, we have done a preliminary analysis of the range of alpha beta TCR gene products in 16 HIV-1-seropositive individuals with normal CD4 counts and in 16 healthy HIV-1-negative controls. Using a panel of monoclonal antibodies with a two-colour direct immunofluorescence method, we found a significant increase in the expression of the V beta 5.3 subfamily in the HIV-positive patient group compared with controls (p less than 0.01). Selected increase in expression of V beta sequences has been described in various autoimmune conditions and our findings raise the possibility that the immunopathological damage from HIV infection may be due to the induction of autoreactivity. If HIV does mimic MHC II, the normal immune response to the virus could represent an autoimmune process similar to graft-versus-host disease.
 ...
PMID:T-cell receptor variable gene products and early HIV-1 infection. 135 71

The induction of major histocompatibility complex (MHC) class II expression in the epithelium of the small intestine of the rat during graft-versus-host disease (GVHD) and the effect of this process on the capacity of isolated epithelial cells to present antigen has been investigated. By immunohistology, increased class II (I-A) was noted in lamina propria cells and villus epithelium and de novo expression in crypt epithelium by Day 7 after transfer of parental spleen cells into irradiated hybrid rats. This increased expression reached a maximum by Day 9 or 10. The kinetics of induction of I-E products paralleled those of I-A in villus epithelium, but I-E was not seen in crypt epithelium. Direct radioimmunoassay of class II in isolated villus and crypt epithelial cells revealed a minor peak of class II, particularly in villus cells, very soon after cell transfer which waned and then increased to a second peak at Days 7-9. Assay of presentation of ovalbumin by isolated enterocytes to primed T cells at the peak of class II induction showed that increased class II expression by villus cells mediated enhanced antigen-presenting activity, whereas increases in crypt cell class II did not enable these cells to present ovalbumin.
 ...
PMID:Induction of MHC class II gene products in rat intestinal epithelium during graft-versus-host disease and effects on the immune function of the epithelium. 155 99

Interleukin-2 (IL-2) therapy generates killer cells with major histocompatibility complex (MHC)-unrestricted cytotoxicity against most tumors but not normal tissues. Cyclosporine A (CsA) has been reported to break tolerance to self and to induce killer cells with specificity against class II MHC (Ia) antigens both on the host and the tumor cells, resulting in a mild graft-versus-host disease (GVHD) in an autologous bone marrow transplantation (BMT) setting in the rat. We used these two agents in a syngeneic BMT model in a strain of mice that does not develop GVHD with CsA. Therapy with either agent alone was ineffective, whereas a combination of CsA plus IL-2 after BMT induced a potent graft-versus-tumor (GVT) effect against a melanoma and an acute myeloid leukemia. The antitumor effect could be adoptively transferred by infusing spleen cells harvested from mice treated with CsA plus IL-2 into secondary recipients that received chemoradiotherapy. The cytotoxicity of these cells was not influenced by treatment of tumor cells with gamma-interferon or Ia antibody. The cytotoxic effect was mediated by Thy 1+ and asialo GM 1+ cells. There was no GVHD either in the primary recipients of CsA and IL-2 or in those receiving the adoptively transferred spleen cells. Our findings show that combination therapy with CsA and IL-2 after syngeneic BMT induces a potent GVT effect in a non-MHC-restricted manner, and point to the existence of differences between the mechanisms of GVT and GVHD.
 ...
PMID:Synergism of interleukin-2 and cyclosporine A in induction of a graft-versus-tumor effect without graft-versus-host disease after syngeneic bone marrow transplantation. 161 Oct 84

It is thought that natural killer cells may play a role in graft-vs.-host reactions after allogeneic bone marrow transplantation, but the use of NK cell-specific reagents has been limited. In this report, an NK allele-specific monoclonal antibody, anti-NK 1.1, was used to study the impact of in vivo donor NK cell depletion on GVH disease, graft-vs.-leukemia (GVL) reactivity and donor T cell chimerism after allogeneic murine BMT. AKR/J (H-2k) recipient mice were preconditioned with suboptimal irradiation (9 Gy = LD50) and transplanted with major histocompatibility complex-matched B10.BR (H-2k) BM cells with or without added spleen cells as a source of T cells. The addition of increasing numbers of spleen cells to the BM inoculum produced GVHD of varying intensities. The beneficial effect of NK depletion on GVHD was dependent on the intensity of the GVH reaction. Donor NK cell depletion had no effect on the survival of mice with severe GVHD after MHC-matched BMT (B10.BR into AKR) or after MHC-mismatched BMT (B10.BR into DBA/2; H-2k into H-2d). However, donor NK depletion increased survival of AKR hosts given sufficient B10.BR splenic T cells to induce mild-to-moderate GVHD. Ex vivo depletion of donor CD8+ T cells also reduced GVH-associated mortality, but the use of both CD8 and NK depletion offered no improvement over either alone, suggesting an interaction between CD8+ and NK 1.1+ cells. In contrast to CD8 depletion, donor NK depletion did not compromise the rapid and complete establishment of donor T cell chimerism nor the ability of chimeras to mount an effective GVL reaction. Thus, elimination of donor NK cells provides an alternate strategy for reducing GVHD without loss of GVL reactivity following MHC-matched allogeneic BMT.
 ...
PMID:A decrease in graft-vs.-host disease without loss of graft-vs.-leukemia reactivity after MHC-matched bone marrow transplantation by selective depletion of donor NK cells in vivo. 163 18


1 2 3 4 5 6 7 8 9 10 Next >>