Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Muromonab-CD3”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1995

In vivo depletion of Thy-1-positive cells originating from normal bone marrow abrogates the suppression of gld disease in normal-gld mixed bone marrow chimeras.

Mice homozygous for gld develop an autoimmune syndrome characterized by hypergammaglobulinemia, massive accumulation of abnormal T cells and the production of autoantibodies. Previous studies in our laboratory have shown that reconstitution of lethally irradiated B6/gld recipients with a mixture of normal and gld bone marrow (BM) suppresses the gld-induced syndrome. In this report we extend this observation by demonstrating that the depletion of normal Thy-1+ cells, but not normal B cells, restores gld disease in mixed BM chimeras congenic for Thy-1 and IgH alleles. These results strongly suggest that normal T cells suppress the development of gld-related abnormalities. It is probable that the mechanism by which normal Thy-1+ cells mediate the suppression is Fas ligand dependent.

Animals↗
PubMed1995

FK 506 rescue therapy for hepatic allograft rejection: experience with an aggressive approach.

Although initial experiences with FK 506 rescue therapy for acute hepatic allograft rejection have provided promising results, analysis of available data indicates that inferior results are obtained when FK 506 rescue therapy is initiated in the latter stages of rejection. Since its initial availability, we have applied an aggressive approach towards FK 506 rescue therapy based on early conversion and assiduous dosing. We have reviewed our experience with this approach in patients with refractory hepatic allograft rejection to provide an assessment of this approach. Sixteen patients were treated for corticosteroid and OKT3-resistant acute hepatic allograft rejection. Fourteen patients were treated for cellular rejection and 2 for humorally-mediated rejection. Median follow-up was 7.3 months posttransplant and 6.0 months post-initiation of FK 506 therapy. Median time to first rejection was 8 days and median time to FK 506 therapy was 29 days. Laboratory values at the time of initiation of FK 506 therapy included: mean serum bilirubin, 4.0 +/- 3.1 mg/dl and SGPT 136 +/- 105 U/l. Prior to FK 506 therapy, patients received an average of 35.5 +/- 19.1 mg/kg of bolus/taper corticosteroids (prednisone equivalent) and 11.25 +/- 4.8 days of OKT3 therapy. FK 506 therapy was successful in reversing all episodes of rejection. Median time to rejection reversal with FK 506 rescue therapy was 23 days (mean +/- SD, 27.6 +/- 16.7 days) in patients with cellular rejection. Time to rejection reversal was 26 and 28 days in the 2 patients with humoral rejection. Patient and graft survival at 6 months were 100%/100%, and 94%/94% at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The antirheumatic drug disodium aurothiomalate inhibits CD4+ T cell recognition of peptides containing two or more cysteine residues.

The mechanism of action of antirheumatic gold drugs, such as disodium aurothiomalate (Au(I)TM), has not been clearly identified. Gold drugs inhibit T cell activation induced by mitogen and anti-CD3 mAb in vitro at relatively high concentrations. However, since gold drugs fail to induce immunosuppression in vivo, the pharmacologic relevance of this finding is doubtful. In this study, we asked whether Au(I)TM interferes with processing and presentation of defined Ags to T cells. Using a panel of murine CD4+ T cell hybridomas, we found that low concentrations of Au(I)TM (< or = 10 microM) led to a markedly reduced IL-2 release of T cell hybridoma clones that recognized peptides containing two or more cysteine (Cys) residues, such as bovine insulin A1-14. Since disodium thiomalate alone had no effect, the inhibition was due to Au(I). IL-2 production induced by anti-CD3 mAb stimulation was not affected by the low concentration of Au(I)TM used. Au(I)TM had no effect on the presentation of peptides containing no or only one Cys residue(s). In contrast to the unmodified insulin peptide A1-14, Au(I) could not inhibit recognition of an insulin peptide in which Cys residues in positions 6 and 11 were replaced by serine. Most likely, the observed inhibition is mediated by formation of chelate complexes between Au(I) and two Cys thiol groups of the affected antigenic peptides. The peptide-specific inhibitory effect of Au(I) on Ag presentation described here might contribute to the therapeutic effect of Au(I) compounds in rheumatoid arthritis.

Amino Acid Sequence↗
PubMed1995

De novo membranous glomerulopathy in renal allografts with unusual histology.

We describe two cases of de novo membranous glomerulopathy in the renal allograft, with unusual histologic findings. In one patient the allograft nephrectomy specimen showed numerous foam cells in the intima of hyperplastic arteries along with prominent features of chronic rejection. In the other patient, prominent IgM deposits were seen in the glomerular mesangium without chronic rejection.

Adult↗
PubMed1995

Effect of calcium-channel blocker on tumour necrosis factor alpha (TNF alpha) production in cyclosporin-treated renal transplant recipients.

PURPOSE OF THE STUDY: The influence of calcium-channel blocker treatment on in-vitro TNF alpha production by peripheral blood mononuclear cells (PBMC) from renal transplant recipients treated with cyclosporin was studied. DESIGN: We compared spontaneous and OKT3-induced TNF alpha production of 12 renal transplant recipients treated with calcium-channel blocker therapy with that of 18 renal transplant recipients who were never treated with a calcium antagonist. RESULTS: The two groups were similar with regards to age, time after transplantation, dosage of immunosuppressive drugs, and blood cyclosporin levels. Spontaneous (481 +/- 161 versus 319 +/- 74 pg/ml, n.s.) and OKT3-induced (745 +/- 182 versus 632 +/- 112 pg/ml, n.s.) TNF alpha production were similar in both groups. CONCLUSIONS: The results indicate that in cyclosporin-treated renal transplant recipients calcium-channel blockers do not affect TNF alpha production.

Adult↗
PubMedDate not supplied

Combined antiviral and immunoglobulin therapy as prophylaxis against cytomegalovirus infection after heart transplantation.

BACKGROUND: Cytomegalovirus is a frequent cause of infection and morbidity after heart transplantation, especially in patients treated with antilymphocytic drugs where the incidence may be as high as 50%. METHODS: To determine the efficacy of combined antiviral and intravenous immune globulin therapy for prevention of cytomegalovirus disease in transplant recipients receiving OKT3 and to compare two different antiviral drug regimens, we reviewed 115 transplant recipients from December 1988 to December 1993 who survived for more than 30 days. Of these, 29 received oral acyclovir for 3 months (group A) and 86 received intravenous ganciclovir for 2 weeks followed by oral acyclovir up to 3 months (group G); all received six infusions of 5% intravenous immune globulin over 2 months. All patients had OKT3 for 10 to 14 days and triple-drug immunosuppression. RESULTS: Cytomegalovirus disease (pneumonitis, gastroenteritis, or leukopenia with fever) occurred in 10% of patients (12 of 115 patients) and was confirmed by positive culture, typical microscopic inclusions, or polymerase chain reaction. In 91 seropositive recipients, there was a trend to less cytomegalovirus disease in group G (3.0%, 2 of 67 patients) than in group A (12.5%, 3 of 24 patients) (p = 0.11), which was more apparent in recipients with seropositive donors where the incidence was reduced from 16.7% (group A) to 2.4% (group G; p = 0.08). In 24 seronegative recipients, cytomegalovirus disease incidence was higher overall and not significantly less in group G (26%, 5 of 19 patients) than in group A (40%, two of five patients) (p = Not significant). CONCLUSIONS: Prophylaxis with combined antiviral and immune globulin therapy produces a low (10%) incidence of cytomegalovirus disease in OKT3-treated heart transplant recipients. In seropositive recipients treated with combined therapy, ganciclovir may be more effective than acyclovir. Larger trials and more aggressive prophylactic strategies are needed in seronegative patients who receive hearts from seropositive donors.

Acyclovir↗
PubMed1995

Critical role of CD28/B7 costimulation in the development of human Th2 cytokine-producing cells.

CD28 is a major costimulatory signal receptor for T cells. We have used human naive CD4+ cells from cord blood to analyze the effect of the CD28/B7 costimulatory pathway on development of T helper (Th) subsets. We show that CD28 costimulation is critical for development of the Th2 cytokine-producing cells and that in the absence of CD28 costimulation, cells are not primed to produce Th2 cytokines and consequently "default" to the Th1 subset, independent of the presence of exogenous cytokines. After CD28 costimulation, cells differentiate into a subset that produces Th2 cytokines. However, further CD28 costimulation is not required to maintain Th2 cytokine production. We conclude that D28 costimulation is critical for the development of Th0 and Th2 subsets, but not for the maintenance of cytokine production.

Animals↗
PubMed1995

Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells.

Cytokine-induced killer (CIK) cells are non-major histocompatibility complex-restricted cytotoxic cells generated by incubation of peripheral blood lymphocytes with anti-CD3 monoclonal antibody (MoAb), interleukin-2 (IL-2), IL-1, and interferon-gamma. Cells with the greatest effector function in CIK cultures coexpress CD3 and CD56 surface molecules. CIK cell cytotoxicity can be blocked by MoAbs directed against the cell surface protein leukocyte function associated antigen-1 but not by anti-CD3 MoAbs. CIK cells undergo release of cytoplasmic cytotoxic granule contents to the extracellular space upon stimulation with anti-CD3 MoAbs or susceptible target cells. Maximal granule release was observed from the CD3+ CD56+ subset of effector cells. The cytoplasmic granule contents are lytic to target cells. Treatment of the effector cells with a cell-permeable analog of cyclic adenosine monophosphate (cAMP) inhibited anti-CD3 MoAb and target cell-induced degranulation and cytotoxicity of CIK cells. The immunosuppressive drugs cyclosporin (CsA) and FK506 inhibited anti-CD3-mediated degranulation, but did not affect cytotoxicity of CIK cells against tumor target cells. In addition, degranulation induced by target cells was unaffected by CsA and FK506. Our results indicate that two mechanisms of cytoplasmic granule release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity proceeds through a cAMP-sensitive, CsA- and FK506-insensitive pathway triggered by yet-to-be-identified target cell surface molecules.

Biomarkers↗
PubMed1995

Induction therapy with cyclosporine without cytolytic agents results in a low incidence of acute rejection without significant renal impairment in heart transplant patients.

Since 1989, the immunosuppressive regimen used in all heart transplant patients at our center has consisted of (i) cyclosporine induction therapy (pretransplant p.o. 2-6 mg/kg depending on serum creatinine level, with immediate post-transplant i.v. therapy at 1-3 mg/h until p.o. therapy alone maintains a whole blood trough level of 300 ng/ml by RIA); (ii) azathioprine (2.5 mg/kg/d i.v./p.o.); (iii) methylprednisolone i.v. for 24 h and then prednisone p.o. at 1 mg/kg/d, tapering to 0.1 mg/kg/d at 1 yr. No prophylactic cytolytic agents (ALG, OKT3) were given. One hundred consecutive patients have been followed for periods of 4-56 months (mean 27 months). The incidence of acute rejection requiring increased therapy was 24%, with only 7% requiring i.v. steroids, 2 of whom (2%) also required ALG and/or OKT3, and with 17% requiring increased oral immunosuppression alone. Mean creatinine levels (mg/dl) were 1.3 pretransplant, 1.4 on d 7, 1.5 at 30 d, and 1.8 after 2 yr. Only 1 patient required temporary hemodialysis. Survival was 98% at 30 d, 94% at 1 yr, and 92% at 2 yr. We conclude that cyclosporine induction therapy with steroids and azathioprine without any cytolytic agent results in a low incidence of acute rejection without jeopardizing renal function.

Acute Disease↗
PubMed1995

Treatment of steroid-resistant graft-versus-host disease after allogeneic bone marrow transplantation with anti-CD3/TCR monoclonal antibodies.

Acute graft-versus host disease (GVHD), one of the major complications of allogeneic bone marrow transplantation (BMT), occurs in 30-50% of all patients transplanted from HLA-identical sibling donors and in 50-80% of all patients transplanted from an unrelated or HLA-mismatched family donor, despite GVHD prophylaxis with methotrexate and cyclosporin. We report our experience with OKT3/BMA031 treatment in 14 patients with severe steroid-resistant GVHD following allogeneic BMT. Three of 5 patients treated in the early post-transplant period with OKT3 remitted and 2 of 3 became long-term survivors. Two patients treated for extensive chronic GVHD showed only minor responses. Five of 7 patients treated with BMA031 showed a partial remission; no complete remission was seen after treatment with this antibody. Shortly after the introduction of OKT3 or BMA031 therapy a rapid decline of the lymphocyte count, especially the CD3+ subset, was observed coinciding with a relative increase of CD56+ lymphocytes and of gamma/delta TCR+ T cells. Increasing numbers of CD3+ lymphocytes preceded recurrence of acute GVHD in three patients. In contrast, persisting CD3-lymphocytopenia was associated with complete clearance of acute GVHD. The incidence of infectious complications following OKT3 or BMA031 therapy was high (42%). Thus, to improve treatment results of severe acute GVHD, prophylactic or pre-emptive strategies are required to reduce the rate of fatal viral and fungal infections.

Acute Disease↗
PubMed1994

Sparing of first dose effect of monovalent anti-CD3 antibody used in allograft rejection is associated with diminished release of pro-inflammatory cytokines.

The murine monoclonal antibody OKT3 is the best known of the anti-CD3 antibodies used for the prevention and treatment of renal allograft rejection. Use of this antibody is associated with improved graft outcome but it has a number of adverse effects thought to result from the massive release of pro-inflammatory cytokines. It has been postulated that OKT3 causes cytokine release because of cross-linking of CD3 molecules on the cell surface by bivalent anti-CD3 antibodies, such as OKT3, and the simultaneous binding of the Fc regions of these monoclonal antibodies to Fc receptors on other cells resulting in cell activation. Monovalent antibodies directed against the CD3 antigen should not, in theory, cause cell activation and cytokine release by this postulated mechanism. This study details the use of a monovalent anti-CD3 monoclonal antibody in the treatment of allograft rejection in five renal transplant recipients and documents the degree of TNF, IFN-g and IL6 release generated after antibody injection. Monovalent anti-CD3 monoclonal antibody reversed the rejection episode for which it was used and was well tolerated in all patients. TNF, IFN-g and IL6 measurement showed that little pro-inflammatory cytokine release occurred after this drug. It is likely that the relative lack of side-effects of monovalent anti-CD3 reflects the blunted release of pro-inflammatory cytokines. Monovalent anti-CD3 monoclonal antibody may be a useful addition to the reagents available to treat allograft rejection.

Acute Disease↗