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)

Regulatory T cells belong to a subset of T lymphocytes which suppress immune reactions in an antigen-specific fashion. They play an important role in the prevention of autoimmune diseases. Ultraviolet (UV) radiation was also found to suppress the immune system in an antigen-specific fashion mediated by UV-induced regulatory T cells. Induction of these cells by UV radiation is an active process which requires antigen presentation by UV-damaged but still viable Langerhans cells in the lymph nodes. UV-induced regulatory T cells have been recently characterized to express CD4 and CD25 and to release the immunosuppressive cytokine interleukin-10 upon activation. Once activated in an antigen-specific fashion, they suppress immune responses in a general fashion via the release of interleukin-10, a phenomenon called bystander suppression. Upon intravenous injection, UV-induced regulatory T cells primarily migrate into the lymph nodes, explaining why they preferentially suppress sensitization. Recently, the development of regulatory T cells was demonstrated in an experimental model of photopheresis, a therapeutic regimen which is used for the therapy of autoimmune diseases, transplant rejection and graft-versus-host disease. Further characterization of these cells will determine whether they can be applied therapeutically in the future with the ultimate aim to induce specific immunosuppression.
 ...
PMID:Regulatory T cells induced by ultraviolet radiation. 1594 74

Graft-versus-host disease is a major complication after allogeneic bone marrow transplantation (BMT) caused by donor T cells. Immunosuppression mediated by CD4(+)CD25(+) regulatory T cells has been shown to ameliorate such pathogenic immune responses in animal models. Here, we summarize recent findings from experimental and clinical studies and propose a model for peripheral tolerance induction after BMT.
 ...
PMID:Immunomodulation after allogeneic bone marrow transplantation by CD4+CD25+ regulatory T cells. 1595 Dec 14

Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.
 ...
PMID:Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion. 1596 5

Haploidentical donors are available for most patients who need allografts but do not have matched donors. However, GVHD, rejection, delayed immune reconstitution, and infections have been significant barriers. We designed a haploidentical BMT protocol focusing on prevention of GVHD and rejection. A total of 53 leukemic patients underwent haploidentical G-CSF-primed BMT without ex vivo T-cell depletion. GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine, methotrexate, and mycophenolate mofetil. In all, 38 patients (the CD25 group) received additional anti-CD25 monoclonal antibody basiliximab. The results were compared to 15 patients who did not receive basiliximab. All patients achieved trilineage engraftment with full-donor chimerism. The incidence of acute II-IV GVHD was 11% in the CD25 group vs 33% in the control group (P=0.046). The overall incidence of extensive chronic GVHD was 15%. T, B, and NK cells recovered within 12 months post transplant. The disease-free survival at 2 years was 53% with a median follow-up of 31 months. In conclusion, G-CSF primed haploidentical BMT along with sequential immunosuppressive agents as described here deserves further study.
 ...
PMID:Anti-CD25 monoclonal antibody (basiliximab) for prevention of graft-versus-host disease after haploidentical bone marrow transplantation for hematological malignancies. 1596 93

In utero hematopoietic stem cell transplantation (IUT) results in limited chimerism and tolerance to alloantigens. We studied the relative role of B7.1 and B7.2 expression by dendritic cells (DCs) in engraftment and in generating donor-specific tolerance in fetal mice. Mature dendritic cells (mDCs) from B7.1(-/-) or B7.2(-/-) donors and wild-type (WT) lineage-depleted (lin(-)) C57BL/6 (B6) bone marrow (BM) were injected into BALB/c fetuses. Six weeks after IUT, B7.1(-/-) recipients had multilineage engraftment (4.7% +/- 0.8% T cells and 5.7% +/- 1.1% granulocytes) associated with graft-versus-host disease (GVHD) and decreased survival, but by 12 weeks only donor CD3(+) cells (2.1% +/- 1.3%) were present. Recipients of B7.2(-/-) mDCs and lin(-) WT B6 BM had exclusively CD3(+)CD4(+) T cells (11.8% +/- 8.5% at 6 weeks and 6.5% +/- 2.5% at 12 weeks). Most of the cells were T-helper 2, although 10.4% +/- 1.4% were of the T-regulatory (T(reg)) phenotype, ie, CD4(+)CD25(+). Donor T(reg) cells were detected both in the thymus and spleen, thus suggesting an effect on both central and peripheral immunity. The animals with T(reg) cells had better survival (82.3% versus 47.4%; P < .01) and no GVHD (0% versus 65%; P < .001). This group alone demonstrated multilineage engraftment of donor hematopoietic cells after postnatal transplantation with megadoses of donor lin(-) BM. Both the engrafted donor CD4(+)CD25(-) and CD4(+)CD25(+) cells induced comparable in vitro suppression of T-cell proliferation, thus suggesting their role in the persistence of the donor T cells in vivo. The CD4(+)CD25(-) cells produced interleukin 10 or interleukin 4 and were inhibited by anti-T-helper 2 cytokine-neutralizing antibodies, whereas the CD4(+)CD25(+) cells showed no evidence of any involvement of a cytokine-like soluble mediator and expressed cytotoxic T-lymphocyte antigen 4 (CTLA-4) and foxp3 constitutively. Donor mDCs and donor CD4 T cells were detected among the thymocytes of the recipients of B7.2(-/-) mDCs and lin(-) WT B6 BM. Thus, it seems that costimulatory molecule expression of donor DCs can play a significant immunomodulatory role in survival, GVHD, engraftment, and homing of allogeneic BM cells after IUT through the generation of T(reg) cells.
 ...
PMID:B7.2-/- mature dendritic cells generate T-helper 2 and regulatory T donor cells in fetal mice after in utero allogeneic bone marrow transplantation. 1612 36

This study was aimed to explore a new method of alleviating graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation through selective elimination of human alloreactive T cells expressing either CD25(+) or CD69(+) by immuno-magnetic cell sorting (MACS). Healthy donor peripheral blood mononuclear cells were cocultivated with bone marrow mononuclear cells from HLA-nonidentical leukemia recipient with remission in one-way mixed lymphocyte culture (OWMLC). After 3 days, both CD25(+) and CD69(+) lymphocytes were removed by MACS. The depleted donor fraction and untreated donor cells were then rechallenged in a secondary mixed lymphocyte culture (MLC) with the original stimulator cells or a third party to assess relative alloreactivity. The results showed that 50% inhibition of the secondary MLC was observed in the depleted donor fraction. Alloreactivity against unrelated third-party cells was largely preserved. It is concluded that this method reduces alloreactivity while retaining reactivity against a third party target in vitro.
 ...
PMID:[Selective depletion of donor alloreactive T cells by using immuno-magnetic cell sorting]. 1612 50

To study if rhesus haploidentical hematopoietic stem cell transplantation model can be established by non-myeloablative conditioning, parent monkeys were used as donors, offspring monkeys were used as recipients. The recipient monkeys received a nonmyeloablative conditioning consisting of fludarabine, cyclophosphamide, total body irradiation and rabbit anti-human thymocyte globulin. Cyclosporine, mycophenolate mofetil and anti CD25 antibody were used for GVHD prevention. Donor mobilized peripheral blood stem cells were transplantated on day 0. Hematopoietic recovery, chimerism level, GVHD were assessed regularly. The results indicated that hematopoietic recoveries in all 4 cases were observed within 8 days after transplantation. Donor hematopoietic chimerism could be induced in all cases, chimerism analysis showed full donor chimerism (FDC) in case 3 and 4, and II to III grade GVHD developed on day 12 and 14. In case 1, only low level donor chimerism was detected on day 7, and transplantation rejection happened eventually. Unfortunately, kidney failure happened in case 2 after conditioning and died several days later, chimerism analysis showed 50% donor rate on day 7. It is concluded that the rhesus transplantation model was successfully established by nonmyeloablative conditioning for striding over the MHC barrier. This rhesus monkey model would provide a basis for future research.
 ...
PMID:[Establishment of rhesus model for haploidentical hematopoietic stem cell transplantation with nonmyeloablative conditioning]. 1612 59

We were interested to analyse the composition of the cellular infiltrate and adhesion molecules expression in the conjunctiva before and at least one hundred days after autologous and allogenic bone marrow transplantation (BMT) and its relation with the presence of dry eye. We used immunohistochemistry on cryopreserved human conjunctiva with monoclonal antibodies to T-lymphocytes (CD3, CD4 and CD8), B-lymphocytes (CD19), macrophages (CD14), natural killer cells (NK, CD57), intercellular adhesion molecule 1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), lymphocyte function associated antigen-1 (LFA-1), very late antigen-4 (VLA-4), interleukin 2 receptor (IL2r, CD25) and HLA-DR. Our autologous recipients had no graft-versus-host disease (GVHD) but allogenic patients had chronic GVHD. After autologous BMT the conjunctiva had significantly more: (1) T lymphocytes (CD3+, CD4+, CD8+) in the epithelium; (2) CD4+ and CD14+ cells in the stroma; and (3) VLA-4 expression in the stroma than before BMT. After allogenic BMT, the conjunctiva exhibited a significant increase of: (1) CD3+ and CD14+ cells in the epithelium; (2) T lymphocytes (CD3+, CD4+, CD8+) and CD14+ cells in the stroma; and (3) VLA-4 and LFA-1 expression in the stroma than before BMT. After the engraftment, the comparison between autologous and allogenic recipients revealed that: (1) there were no significant differences in adhesion molecule expression; (2) the epithelium of autologous recipients had significantly more CD3+ cells; and (3) the stroma of allogenic patients had significantly more CD3+ and CD8+ cells. Among allogenic recipients, CD14+ cells were significantly increased both in the epithelium and in the stroma of patients with signs or symptoms of dry eye in comparison with patients without ocular involvement. Additionally, those having keratoconjunctivitis sicca (KCS) had CD4/CD8 ratios significantly higher than those without KCS. In conclusion, in the conjunctiva after autologous BMT a subclinical cell mediated immune reaction seems to take place. The conjunctivitis of chronic GVHD is complex, with T cells and macrophages dramatically contributing to the process.
 ...
PMID:Cell populations and adhesion molecules expression in conjunctiva before and after bone marrow transplantation. 1612 99

In the 1980s, attempts were made to use placenta-eluted gamma globulins (PEGG) in patients with graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). Because production of PEGG had been discontinued for many years, we aimed to reestablish a method of production and further explore the mechanisms of the effect of these globulins on GVHD. PEGG were prepared by elution at acid pH from extensively washed human placenta followed by precipitation with saturated ammonium sulfate and absorption on a protein A Sepharose column. In vitro study showed PEGG significantly inhibited both the proliferative response of T-cells to phytohemagglutinin (PHA) and the mixed lymphocyte reaction (MLR). Results of flow cytometric analysis indicated that PEGG down-regulated the expression of CD25 and CD69 on T-cells stimulated by PHA. Cytokine quantification in MLR supernatant showed that PEGG decreased secretion of interferon 3 (IFN-3) but increased production of interleukin 4. In a murine GVHD model, we investigated the preventive effect of PEGG on lethal GVHD in irradiated recipients of allogeneic bone marrow cells and spleen cell transplants by in vivo administration. Compared with controls, recipients treated with PEGG had a markedly increased survival rate with less histopathological evidence of GVHD. These results suggest that PEGG may be a potent therapeutic agent for GVHD.
 ...
PMID:Purification of placenta-eluted gamma globulins and their strong effect against graft-versus-host reactions in vitro and in vivo. 1614 51

Despite substantial advances in our understanding of CD4+ CD25+ regulatory T cells, a possible equivalent regulatory subset within the CD8+ T cell population has received less attention. We now describe novel human CD8+/TCR alphabeta+ T cells that have a regulatory phenotype and function. We expanded and cloned these cells using autologous LPS-activated dendritic cells. The clones were not cytolytic, but responded in an autoreactive HLA class I-restricted fashion, by proliferation and production of IL-4, IL-5, IL-13 and TGFbeta1, but not IFN-gamma. They constitutively expressed CD69 and CD25 as well as molecules associated with CD4+ CD25+ regulatory T cells, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and Foxp3. They suppressed IFN-gamma production and proliferation by CD4+ T cells in vitro in a cell contact-dependent manner, which could be blocked using a CTLA-4-specific mAb. They were more readily isolated from patients with ankylosing spondylitis and may therefore be up-regulated in response to inflammation. We suggest that they are the CD8+ counterparts of CD4+ CD25+ regulatory T cells. They resemble recently described CD8+ regulatory cells in the rat that were able to abrogate graft-versus-host disease. Likewise, human HLA-restricted CD8+ regulatory T cells that can be cloned and expanded in vitro may have therapeutic applications.
 ...
PMID:Autoreactive human peripheral blood CD8+ T cells with a regulatory phenotype and function. 1618 Feb 49


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