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Biomedical subjects

C Reiter

Publications and source records attributed to C Reiter.

At least 19 recordsLinked to original sources
PubMed1992

Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the alpha-chain of the human interleukin-2 receptor.

The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the alpha-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2R alpha chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy.

Amino Acid Sequence↗
PubMed1992

The monoclonal CD4 antibody M-T413 inhibits cellular infection with human immunodeficiency virus after viral attachment to the cell membrane: an approach to postexposure prophylaxis.

Infectious cellular uptake of human immunodeficiency virus (HIV) is initiated by a complex sequence of interactions between the viral envelope gp120/gp41 complex and the cellular CD4 receptor resulting in the exposure of a hydrophobic region of gp41 that mediates the irreversible fusion of the virus with the cell membrane. Here we show that viral penetration into a susceptible cell can be inhibited by the high-affinity monoclonal CD4 antibody (CD4 mAb) M-T413 even when it is added as late as 30-120 min after the initial contact of virus with the cell membrane. Inhibition of infection was assessed by monitoring cultures for 34 days after exposure to virus using four different methods simultaneously, including detection of viral DNA by PCR. The interval during which HIV remains sensitive to postbinding neutralization by CD4 mAb depends on strain of virus and type of target cell. Preparations of recombinant soluble CD4 (and the immunoadhesin CD4-IgG1) were much less efficient when compared with mAb M-T413, particularly in blocking infection by fresh HIV-1 isolates. Also cellular transmission of HIV, as determined by syncytia formation within 24 hr, was prevented by mAb M-T413 when added within 45 min of contact of infected H9 cells with uninfected C8166 cells. Together with the favorable clinical experience obtained with CD4 mAbs as immunomodulatory drugs, these data suggest that infusion of CD4 mAb M-T413 may be a therapeutic modus for immediate prophylactic intervention after occupational exposure to HIV and for prevention of intrapartum mother-to-infant HIV transmission.

Animals↗
PubMed1992

Antibody and HIV-1 gp120 recognition of CD4 undermines the concept of mimicry between antibodies and receptors.

It has been proposed that antibodies can mimic the binding of a receptor to its ligand and that anti-idiotype antibodies raised against such antibodies can be used to identify the receptor. A large number of antibodies have been raised against CD4, the receptor on T cells for the envelope glycoprotein gp120 of the human immunodeficiency virus, and the site at which gp120 binds to CD4 has been delineated. It has therefore become possible to contrast the fine specificities of a natural ligand (gp120) and antibodies that interact with the receptor at the same site. Here we report that out of a panel of 225 anti-CD4 antibodies, only one showed fine binding specificity that was broadly like that of gp120, but the evidence was against this being an exact mimic. Thus the data indicate that the production of antibody mimics will occur very rarely or not at all and that the anti-idiotype approach is unlikely to be useful. This contention is supported by a review of the results of attempts to use this approach. Taking strict criteria for success, there is no example for which the anti-idiotype approach has led to the discovery of a previously undescribed receptor or other protein of interest.

Animals↗
PubMed1992

Persistent depletion of CD4+ T cells and inversion of the CD4/CD8 T cell ratio induced by anti-CD4 therapy.

A 49-year-old patient with refractory rheumatoid arthritis was treated repeatedly with anti-CD4 murine monoclonal antibodies. While the first anti-CD4 treatment resulted in a marked, however transient, depletion of CD4+ cells from 1070 to a minimum of 175/microliters, a second treatment cycle resulted in a persistent decrease. Despite this marked depletion, no major clinical improvement occurred, which was in striking contrast to other patients treated in a similar way. Of interest, the administration of low doses of chlorambucil led to significant clinical benefits. Markedly reduced numbers of CD4+ cells (200-500/microliters) were observed for more than 2 years, while the numbers of CD8+ cells increased after the second treatment. No infectious episodes occurred. Discontinuation of chlorambucil did not lead to increasing amounts of CD4+ cells. In contrast to the rapid reduction of CD4+ cells from the blood stream induced by anti-CD4 infusions, there was a considerable delay until altered CD4/CD8 ratios were observed in intraarticular sites. No evidence was found for either humoral or cellular immune reactivities towards CD4+ T helper cells. Our findings suggest that in certain patients undergoing anti-CD4 therapy there may be a reduced capacity of the CD4+ T helper cell pool to regenerate.

Antibodies, Monoclonal↗
PubMed1991

Treatment of rheumatoid arthritis with monoclonal CD4 antibody M-T151. Clinical results and immunopharmacologic effects in an open study, including repeated administration.

Recent experimental and clinical data point to the T helper lymphocyte subset as playing a central role in the pathogenesis of rheumatoid arthritis (RA). Thus, a therapeutic strategy aimed specifically at the CD4 T cell subset is warranted. We treated patients with active RA for 7 days with a daily dose of 20 mg of CD4 monoclonal antibody M-T151, administered intravenously over 30 minutes. There were no negative side effects. According to changes in the combined parameters of Ritchie articular index, pain assessment, grip strength, and morning stiffness, 6 patients had a good response. Clinical improvement was greatest approximately 2 weeks after termination of the therapy and lasted from 4 weeks to 6 months. Of the serologic parameters of inflammation, only the C-reactive protein level improved in the patients with a favorable response. Close immunologic monitoring revealed a transient, selective depletion of CD4+ T cells after each infusion. During the entire treatment period, residual circulating CD4+ cells were found to be coated with CD4 antibody, whereas free antibody was detected in the serum only for approximately 8 hours after each infusion. Immediately after infusion, soluble CD4 antigen appeared in the serum. In addition to the cell-bound CD4 antibody, complement components could be detected on the surface of the remaining CD4+ cells. The proliferative response of peripheral blood mononuclear cells to purified protein derivative was significantly diminished 4 weeks after cessation of antibody treatment. Six patients showed a weak antibody response to mouse immunoglobulin. In 4 of the responders who received a second course of therapy (2 of them as outpatients), a therapeutic effect was noted that was similar to that after the first course. Only 1 patient, who had low titers of serum IgE anti-mouse Ig antibodies, showed a mild anaphylactic reaction at the end of the second course of therapy. Treatment of RA with the monoclonal CD4 antibody M-T151 seems to be a promising alternative, although the optimal dose and the regimen of administration are still to be defined.

Animals↗
PubMed1991

[The finishing of the bristle ends in interdental brushes].

The result of a scanning electron microscopic study of fourteen interdental brushes, available on the German and Swiss market, was that all products have an insufficient finish of bristle ends. Only one brush showed 17.3% of acceptably rounded bristle ends. In addition, the unacceptable rounded bristle ends were classified, corresponding to their variation of form. The results allowed to estimate the degree of damaging potential of the periodontal tissues, using interdental brushes.

Equipment Design↗
PubMed1989

Deposition of complement activation products on plastic-adsorbed immunoglobulins. A simple ELISA technique for the detection of defined complement deficiencies.

The activation of complement components in human serum has been studied using immunoglobulins adsorbed to microtiter plates. The sequential deposition of complement fragments was detected by a series of mono- and polyclonal antibodies in an indirect enzyme-linked immunosorbent assay (ELISA). Antibodies against C1q, C1s, C4b/d, C3b/d, factor B, C5b-9 membrane attack complex (MAC), the regulatory complement proteins C4 binding protein (C4bp) and properdin were reactive. Several lines of evidence suggest that complement activation was via the classical pathway: (1) complement activation was highly isotype-restricted with regard to the adsorbed Igs (human IgG1 and IgG3 as well as mouse IgM, IgG2a and IgG2b isotypes are strong activators in contrast to human IgG2, IgG4, IgA and mouse IgG1); (2) Ca2+ depletion, heat treatment (56 degrees C for 45 min), incubation with 0.5 M KSCN or heat-aggregated immunoglobulins (aggIgG) abrogated serum activity; (3) complement deficient sera (C1q def', C2 def', C6 def' human sera; C2 def', C4 def' guinea pig sera) showed impaired deposition of the complement components that follow the missing component in the cascade of activation. In a clinical study sera from patients with systemic lupus erythematosus (SLE) were investigated in order to measure the effect of hypocomplementemia due to complement consumption. The results obtained suggest that this new and simple assay is well suited for (1) the detection of various inherited complement deficiencies, (2) the semiquantitative evaluation of sera with decreased complement levels, (3) a more detailed study of complement components bound to a solid phase.

Adsorption↗
PubMed1989

Primary peripheral T cell lymphoma in a kidney transplant under immunosuppression with cyclosporine A.

A 56-year-old patient received a cadaveric renal allograft because of primary cystic kidney disease. The donor was a 28-year-old man who died from head trauma. No other major illnesses were present at the time of transplantation. Immunosuppression was performed with cyclosporine A and steroids. After 3 months, the patient presented with fever and abdominal pain which was located in the region of the allograft. Ultrasonography demonstrated a tumor mass at the renal transplant hilus that was suspected to be an infected hematoma. Kidney biopsy from the cortex revealed only severe morphologic signs of cyclosporine A toxicity which was due to high cyclosporine A levels during the first 2 months after transplantation. The patient died from pulmonary embolism 6 months posttransplant. Histologic evaluation of the tumor specimens obtained at autopsy showed an extensive infiltration of the renal hilus and the medulla by a peripheral T cell lymphoma of the large-cell type. The T cell origin was confirmed by immunohistochemistry using the T cell-associated monoclonal antibodies UCHL-1 and MT1.

Adult↗
PubMed1989

Anti-CD4 antibody treatment of patients with rheumatoid arthritis: I. Effect on clinical course and circulating T cells.

Eight patients with arthritis (seven with rheumatoid, one with psoriatic arthritis) were treated for 7 d with a daily injection of 10 mg of mouse monoclonal anti-CD4 antibodies (three with VIT4, five with MT151). With the exception of a short-lasting low-grade fever in one patient, no side effects were observed. Clinical symptoms (morning stiffness, number of swollen joints, pain assessment and Ritchie articular index) improved in all patients within 7 d of treatment. Improvement lasted from 3 weeks to greater than or equal to 5 months (mean approximately 11 weeks). Rheumatoid factors, immune complexes and other laboratory parameters did not change during or after treatment. Skin reactivity to recall antigens was suppressed in four out of six patients during treatment but returned to pretreatment levels within 6 weeks. Immunofluorescent analysis revealed a short-lasting drop of T cells, mainly of the CD4+ CDw29+ subset, but monocytes were also affected. The injected antibody was detectable on circulating cells for about 10 h. Within 20-24 h, the cell distribution returned to pretreatment levels. In six out of eight patients an anti-mouse-Ig response was seen. We conclude that mouse anti-CD4 monoclonal antibody (MoAb) treatment is well tolerated and that the cellular immunological changes observed are short-lasting. The low incidence of side effects may justify further clinical studies to evaluate the clinical efficacy of such treatment.

Antibodies, Anti-Idiotypic↗