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Biomedical subjects

M Jonker

Publications and source records attributed to M Jonker.

At least 109 records · Page 6Linked to original sources
PubMed1986

Differentiation antigens on rhesus monkey lymphocytes. II. Characterization of RhT3, a CD3-like antigen on T cells.

A monoclonal antibody FN18 is described, which is specific for mature rhesus monkey T lymphocytes. It defines a cell surface antigen, composed of two polypeptide chains with a molecular mass of 22 and 27 kDa. In view of these and other similarities with the human T3 or CD3 antigen, it was designated as RhT3. Expression, distribution and certain functions of RhT3 were compared with those of its human counterpart. Analogous to anti-CD3 antibodies in man, FN18 is able to modulate its target antigen, has mitogenic properties and is able to block the pokeweed mitogen and concanavalin A-driven cell proliferation, but not that caused by phytohemagglutinin. In spite of such minor dissimilarities the available data strongly suggest that the RhT3 antigen is the rhesus monkey's homologue of the human CD3 antigen.

Animals↗
PubMed1986

The influence of OKT8F treatment on allograft survival in rhesus monkeys.

The immunosuppressive effect of a monoclonal antibody specific for the cytotoxic/suppressor T cells (CD8) was investigated in rhesus monkeys. This antibody (OKT8F) removed the CD8-positive T cells from the circulation and prolonged skin allograft survival. Since most patients awaiting a kidney allograft are transfused prior to transplantation, the immunosuppressive potency of OKT8F was subsequently investigated in transfused recipients. No significant prolongation of the mean survival time was observed when OKT8F was given prophylactically. However, no early rejections were observed, while 30% of the control animals rejected their kidneys within 2 weeks. This might indicate that OKT8F prevents early rejection of a kidney allograft in transfused recipients.

Animals↗
PubMed1985

Enumeration of (auto)antibody producing cells in human using the "spot-ELISA".

An enzyme-linked immunosorbent assay (spot-ELISA) for individual immunoglobulin secreting cells, which became recently available, was applied to the enumeration of human B lymphocytes secreting specific antibodies of thyroglobulin. Polyclonally activated B cells from patients with auto-immune thyroid disease are incubated in thyroglobulin coated plates. After removal of the cells specific antibodies are visualized by means of an immunoenzyme technique employing agarose to localize converted substrate. Individual specific antibody secreting cells are counted as blue spots using an inverted microscope. Numbers and isotype of spots correlate well with the amount and isotype of secreted antibody as detected with a conventional ELISA. This easy to perform, complement-independent technique offers a useful alternative to conventional plaque forming cell assays.

Antibody-Producing Cells↗
PubMed1985

OKT4 and OKT4A antibody treatment as immunosuppression for kidney transplantation in rhesus monkeys.

A mixture of OKT4+4A monoclonal antibodies (reactive with T4 cells) was tested for its immunosuppressive potential in rhesus monkeys receiving a kidney allograft. The kidney transplant model used in this study was designed to mimic the clinical situation. Therefore, all animals received a low dose of azathioprine and prednisolone, and the effectiveness of monoclonal antibody treatment was assessed in nontransfused and transfused recipients. The treatment very effectively suppressed acute graft rejection in untransfused recipients. In transfused recipients, which show an improved graft survival, no additional favorable effect of OKT4 + 4A treatment was seen when this treatment was given at the time of transplantation. It is possible that transfused recipients that reject their kidney in an acute fashion do not benefit from the OKT4 + 4A treatment because they have generated primed effector cells that belong to a T4-negative subpopulation or a T4-positive subpopulation with high affinity for donor cells. When the OKT4 + 4A treatment was given at the time of graft rejection in transfused recipients, thus treating chronic rather than acute rejection, a modest improvement in graft survival was observed. It seems, therefore, that anti-T4 antibodies will be of limited value for clinical transplantation and should be used in combination with other immunosuppressive drugs.

Animals↗
PubMed1983

The effect of in vivo application of monoclonal antibodies specific for human cytotoxic T cells in rhesus monkeys.

Rhesus monkeys were treated in vivo with monoclonal antibodies specific for human cytotoxic T cells. These antibodies reacted with rhesus lymphocytes as they do with human lymphocytes. Injection of a pool of monoclonal antibodies resulted in rapid elimination of the relevant T cell subpopulation from the circulation. Injection of a single monoclonal antibody did not result in elimination of the subpopulation, but the cells were coated with the injected monoclonal antibody. Injection of the single monoclonal antibody did not prolong the allogeneic skin graft. These results indicate that the rhesus monkey is a useful model for testing antihuman monoclonal antibodies.

Animals↗
PubMed1983

Effects of in vivo administration of monoclonal antibodies specific for human T cell subpopulations on the immune system in a rhesus monkey model.

Monoclonal antibodies specific for human T cell subsets have been tested for their immunosuppressive effect in a rhesus monkey skin graft model. Rhesus monkeys were injected i.v. daily with antibodies specific for helper T cells (OKT4 and 4A), for cytotoxic/suppressor T cells (OKT8A), or all peripheral T cells (OKT11A), and they received an allogeneic skin graft one or two days after the initial antibody treatment. The OKT4, 4A, and 11A antibodies prolonged skin graft survival, but OKT8A did not. All animals were carefully monitored regarding levels of T cell subsets and antibody formation to the injected monoclonal antibody. The relevant T cell subset was not eliminated from the circulation when OKT4 and OKT4A antibodies were given separately. The OKT4+ cells remained in the circulation coated with antibody. OKT4+ cells could no longer be demonstrated when both OKT4 and 4A were given simultaneously. However, this difference in effect on the OKT4+ cells did not influence skin graft survival time. All animals receiving monoclonal antibody treatment developed antimouse-Ig antibodies after 10 to 13 days of treatment, which presumably counteracted the effect of the antibodies. From these data it appears that the rhesus monkey is a useful animal model in which to investigate the potential of monoclonal antibodies against human lymphocyte subpopulations to modify and regulate the immune response in an orderly fashion.

Animals↗
PubMed1982

Typing for RhLA-D in rhesus monkeys: I. Characteristics of ten groups of homozygous typing cells.

Certain characteristics of 38 homozygous typing cell (TC's) of rhesus monkeys were determined. These TC's define ten RhLA-D locus specificities. Eight of them are associated with established RhLA-DR antigens. Two other groups of typing cells, D9 and D10, were previously considered to be associated with "blank" antigens of the DR series; they now appear to be associated with B-cell antigens which are also likely to be controlled by the DR locus. No influence of RhLA-A or B antigens of MLC reactivity was observed. It was shown, however, that products of at least one locus other than D/DR is responsible for MLC stimulation. Whether those MLC antigens are associated with serologically identifiable B-cell antigens which are not controlled by the DR locus, is not yet clear.

Animals↗
PubMed1982

Typing for RhLA-D in rhesus monkeys: II. Genetics of the D antigens and their association with DR antigens in a population of unrelated animals.

A population of 94 unrelated rhesus monkeys was typed for MLC antigens using 38 homozygous typing cells which define RhLA-D specificities. A genetic analysis showed that the ten D specificities are alleles of a single locus, the gene frequencies of which are in Hardy-Weinberg equilibrium. The association between the cellularly defined D and the serologically defined DR antigens in the population was usually high, confirming the close relationship between D and DR antigens. Two new associations were found, i.e. between the D-locus antigens 9 and 10 and the serologically defined B-cell antigens 109 and 101, respectively. This observation confirms prior speculations that the latter two antigens may belong to the DR series.

Alleles↗
PubMed1981

Acute bleeding varices: a five-year prospective evaluation of tamponade and sclerotherapy.

In a five-year study of massive upper gastrointestinal hemorrhage, 143 patients had esophageal varices diagnosed on emergency endoscopic examination. Seventy-one patients had active bleeding from varices and required Sengstaken tube tamponade during at least one hospital admission. The remaining patients included 33 with variceal bleeding which had stopped and 39 who were bleeding from another source. Sixty-six of the former group of 71 patients were referred for emergency injection sclerotherapy. These 66 patients were followed prospectively to August 1980, and had 137 episodes of endoscopically proven variceal bleeding requiring Sengstaken tube control followed by injection sclerotherapy during 93 separate hospital admissions. Definitive control of hemorrhage was achieved in 95% the patients admitted to the hospital (single injection 70%; two or three injections 22%). The death rate per hospital admission was 28%. No patient died of continued variceal bleeding, and exsanguinating variceal hemorrhage no longer poses a major problem at our hospital. The combined use of initial Sengstaken tube tamponade followed by injection sclerotherapy has simplified emergency treatment in the group of patients who continue to bleed actively from esophageal varices, despite initial conservative treatment.

Acute Disease↗
PubMed1981

Mixed lymphocyte reactivity in chimpanzees. II. Family studies and identification of D locus antigens.

A large number of related chimpanzees were tested in mixed lymphocyte cultures against each other. Several similarities among the D locus products coded for by different ChLA haplotypes were observed. Six animals were found to be homozygous for D locus antigens and two of these animals carried the same D specificity. Hence, the available "typing cells" permitted the identification of five D locus antigens of the chimpanzee. So far, no linkage disequilibrium has been found between any of the D locus antigens and ChLA-A or -B locus antigens.

Animals↗
PubMed1980

Mixed lymphocyte reactivity in chimpanzees. I. Some technical and genetic aspects.

One-way mixed lymphocyte culture (MLC) tests were performed among the members of five chimpanzee harems in all possible combinations: parents, parent-child, siblings and half-siblings. The technical aspects of MCL testing in chimpanzees appeared to be very similar to those observed for human and rhesus monkey MLC's. Two unexpected observations were made for which no satisfactory explanation can as yet be give: firstly, the occurrence of animals with consistently high autologous values and secondly, the existence of chimpanzees displaying low MLC responsive. The high autologous values occurred mostly in older imported animals (25% with high autologous values), while only one of the 45 laboratory born animals showed this phenomenon. Low responsiveness occurred in a few offspring belonging to a single harem only and is therefore likely to be genetically controlled but, as it appeared, not by genes linked to ChLA. Data suggesting the existence of an MHC-linked "major MLC" or D locus were confirmed and extended. A gene dose effect for D locus antigens was demonstratable, i.e., combinations of related animals differing for one showed lower MLC responses than combinations differing for two ChLA haplotypes. The number of D locus alleles was estimated to be 10.

Animals↗
PubMed1980

Possible mechanisms by which alloantisera inhibit in the MLC test.

MLC inhibition studies were performed with two human alloantisera: one specific for HLA-B7, the other for HLA-DRw7. The stimulator cell inhibitory effects of these sera were tested in primary and secondary MLC tests. Both sera inhibited in the primary MLC, whereas only the anti-DRw7 serum was capable of blocking the secondary MLC test. The difference in inhibiting properties of these sera was further analyzed in primary MLC tests using selected MLC combinations, Fc receptor negative cell populations and pepsin digests of the anti-B7 serum. Anti-DRw7 antibodies could inhibit by masking the stimulatory DR antigens. The inhibition of the anit-B7 antiserum was dependent on Fc, which suggested that anti HLA-B antibodies inhibited by some other mechanism. This inhibition could have been caused by antibody dependent cellular lympholysis of the stimulator cells or by the induction of suppressor cell activity.

Antibody Specificity↗
PubMed1980

HC restricted dual specific inhibition of mixed leukocyte culture reactions by human HLA antibody molecules.

A human alloantiserum was found which selectively inhibits responding cells in mixed leukocyte culture reactions. Inhibition was achieved by pre-incubation of responder cells in the antiserum followed by washing. The serum showed dual specificity as an inhibiting agent. First, inhibition was restricted to HLA-B7 or -B40 positive stimulator cells, specificities against which the antiserum also had cytotoxic activity. Second, inhibition was almost exclusively associated with the presence of the phenotype HLA-A1, -B8 on the responder cells The HLA associated specificity for responder cells was unexpected since no alloantibody activity directed to responder alloantigens could be detected by conventional serological-methods. The antiserum donor had not been immunized with HLA-A1, -B8 antigens nor with known crossreactive antigens. Furthermore, the serum donor did not carry HLA-A1, -B8 antigens herself. The inhibiting substance in the antiserum had physicochemical properties of IgG and was specifically reactive with HLA-B7 positive platelets. Pepsin digest preparations were not inhibitory. Fc receptor positive responder cells were required for inhibition. Responder cells, preincubated with the antiserum, suppressed the response of cells not incubated with the antiserum. Three possible explanations of these results are discussed: specific binding of the Fc part of the antibody with Fc receptors of responder cells, specific activation of suppressor cells and cross-reactivity.

Antibody Specificity↗
PubMed1979

Influence of matching for HLA-DR antigens on skin graft survival.

HLA-DR typing results of 47 skin transplant donor-recipient pairs were analysed. HLA-A, B, and C typing and mixed lymphocyte culture (MLC) testing was also included in this study. Skin transplants exchanged between HLA-A-, B-, and DR-identical, MLC-negative donor-recipient pairs had the longest graft survival (mean survival time, 17 days), whereas skin grafts exchanged between completely nonidentical donor-recipient combinations had the shortest survival (mean survival time, 10 days). Because of the correlation between identity for the DR antigens and the low or nonreactivity in the MLC test, identity for DR will predict a better skin graft survival than nonidentity. It was concluded that the best match between donor and recipient of a graft, using only serological techniques, is one where there is identity for HLA-A, B, and DR.

B-Lymphocytes↗
PubMed1979

Human skin grafts from mixed lymphocyte culture-positive donors provide help for the rapid rejection of simultaneously transplanted skin grafts from mixed lymphocyte culture-negative donors.

The influence of grafting more than one skin transplant simultaneously on one recipient was investigated. When a mixed lymphocyte culture (MLC)-negative skin was transplanted along with an MLC-positive skin, the MLC-negative skin survived for a significantly shorter time than when transplanted alone. This indicated that the MLC-positive skin provided a stimulus that could provide help to reject the MLC-negative skin. This finding might be important clinically. When an MLC-negative transplant is given to a patient, one should not transfuse this patient with MLC-positive leukocyte-rich blood.

Graft Rejection↗