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M Jonker

Publications and source records attributed to M Jonker.

At least 37 records · Page 2Linked to original sources
PubMed1998

Collagen-induced arthritis in rhesus monkeys: evaluation of markers for inflammation and joint degradation.

The objective of this study was to analyse parameters in rhesus monkey collagen-induced arthritis (CIA) with which the inflammation and destruction of the joints can be described in quantitative terms. CIA was induced in genetically susceptible and resistant monkeys, which can be distinguished on the basis of the dominant resistance marker Mamu-A26. The disease course was monitored daily using a semiquantitative scoring system. Plasma samples were collected once or twice weekly and analysed for C-reactive protein (CRP). Urines were collected overnight once a week and analysed for excretion rates of the collagen cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). The results show that periods of active CIA are characterized by substantial weight loss and increased plasma CRP levels, followed shortly thereafter by increased excretion rates of the collagen cross-links HP and LP. Remission of the disease can be recognized by a decline in plasma CRP levels and especially an increase in body weight. The highest CRP levels were found in the most severely arthritic monkeys, indicating a possible relationship of the absolute plasma CRP levels to the severity of inflammation. During periods of active arthritis, increased excretion rates of collagen cross-links HP and LP in the urine were found. In particular, the major collagen cross-link in articular cartilage, HP, showed a strong increase (9- to 15-fold). The excretion rates of LP, which is considered as a bone-specific degradation marker, only increased 4- to 6-fold, thus indicating predominant destruction of cartilage and less of bone. In conclusion, the severity of CIA can be monitored in a quantitative manner using plasma CRP levels, urinary excretion rates of HP and LP, and body weights, superimposed on semiquantitative clinical scores. The parameters also facilitate a more objective assessment of the effect of anti-arthritic drugs in the model than with the clinical scores alone.

Amino Acids↗
PubMed1998

Characterization of the ABO blood group genes in macaques: evidence for convergent evolution.

The ABO blood group system is known to act as a major transplantation barrier in primates. Different primate species share the presence of A and B antigens. The polymorphism of the macaque ABO blood group genes was analyzed by cloning and sequencing the exon 7 region. In the case of the rhesus macaque (Macaca mulatta) and cynomolgus monkey (Macaca fascicularis) we were able to identify ABO blood group gene segments which cluster into two lineages, namely: *A/*O1 and *B. In addition allelic variation was observed. The 2 amino acid replacements at positions 266 and 268, which are thought to be crucial for A or B transferase activity, could be confirmed for both macaque species. Comparison of primate sequences shows that A and B reactivity was generated independently from each other in the hominoids and Old World monkey lineages. Hence, the primate A and B blood group genes are subject to convergent evolution.

ABO Blood-Group System↗
PubMed1997

Flow cytometric analysis on reactivity of human T lymphocyte-specific and cytokine-receptor-specific antibodies with peripheral blood mononuclear cells of chimpanzee (Pan troglodytes), rhesus macaque (Macaca mulatta), and squirrel monkey (Saimiri sciureus)

There are relatively few monoclonal antibodies (mAb) that have been characterized for their applicability in studies on the immune system of various nonhuman primates. In the present study, we identified a large number of mAb that can be used in future immunological studies in three different nonhuman primates, i.e., chimpanzees, rhesus macaques, and squirrel monkeys. The reactivity of 161 anti-human mAb to T-cell antigens and cytokine receptors were tested on peripheral blood mononuclear cells (PBMC) from the three primate species by flow cytometric analysis. A total of 105 (65%), 73 (45%), and 68 (42%) antibodies reacted with PBMC from chimpanzees, rhesus macaques, and squirrel monkeys, respectively. Out of the 161 mAb, 38 reacted with all three species and 112 reacted with one or two of the species. No specific reaction was observed with mAb to receptors to GM-CSF, 4-1BB, FLT3, FLX2, common beta-chain, IL-1 (type I receptor), and IL-8.

Animals↗
PubMed1997

Encephalitogenic potential of myelin basic protein-specific T cells isolated from normal rhesus macaques.

Myelin basic protein (MBP)-specific T cells are implicated in the pathogenesis of multiple sclerosis and are targets of selective immunotherapies. However, autoantigen-specific T cells can also be isolated from healthy individuals. Their functional potential is unknown and obviously cannot be tested in humans. We approached this question in a closely related primate species, the rhesus monkey. CD4+ T cell lines specific for MBP were isolated from normal rhesus monkeys using the same primary limiting dilution technique that is now widely used to generate human autoreactive T cell clones in vitro. Three different epitopes were recognized by three rhesus T cell lines isolated from three different monkeys. Upon activation, all lines produced interferon-gamma, interleukin-2, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor but neither interleukin-4 nor transforming growth factor-beta. The MBP-specific T cells were injected intravenously without adjuvant into the nonirradiated autologous monkey. One of the three rhesus monkeys developed an encephalomyelitis with a pleocytosis in the spinal fluid and perivascular infiltrates in the leptomeninges, spinal nerve roots and cerebral cortex. The data demonstrate that the normal immune repertoire of a primate species contains MBP-specific CD4+ T cells that are able to induce an autoimmune encephalomyelitis upon transfer into the nonirradiated autologous recipient.

Animals↗
PubMed1996

Complete withdrawal of immunosuppression in allograft recipients. A study in rhesus monkeys.

The influence of pretransplant blood transfusions on kidney allograft survival after cessation of immunosuppressive treatment was studied in 11 rhesus monkeys. The animals were conditioned by three pretransplant blood transfusions. After an induction treatment with cyclosporine (CsA), the immunosuppression was stopped and the natural course of the graft was followed. In two monkeys long-term graft survival without immunosuppression was obtained (2.5 and 4.25 years). In a third monkey, permanent allograft acceptance was achieved after complete cessation of immunosuppression. The monkey is still alive with a well-functioning graft for more than 13 years after cessation of immunosuppression. This monkey had received CsA for 12 months, two MHC DR-matched blood transfusions, and no repeated mismatches between graft and blood transfusion donors. We speculate that blood transfusions may influence allograft function in two opposite ways. As reported previously in man, MHC class-II-matched transfusions appear to beneficially influence allograft survival. This effect seems to be negated by a mismatched MHC class II antigen in the blood transfusion donor which is also present in the organ donor -- a so-called repeated mismatch. Further studies in rhesus monkeys are required to confirm and extend these results. In the future, these observations might help in developing a protocol that opens up the possibility of cessation of immunosuppression in transplant patients.

Animals↗
PubMed1996

A new reagent for the induction of T-cell depletion, anti-CD3-CRM9.

We have developed a new reagent for inducing in vivo T-cell depletion and have tested this reagent in rhesus monkeys. The reagent is an anti-CD3 epsilon immunotoxin based on a diphtheria toxin binding-site mutant, CRM9. After administration to monkeys, T cells are depleted from both the blood and lymph node compartments to < 1% of their initial values. T-cell depletion is associated with transient immunosuppression, as judged by delayed rejection of RhLA-mismatched skin allografts. T cells are repopulated in both compartments; however, the rate of repopulation is age dependent. The rate is rapid in juvenile animals (12 days) and requires > 30 days in old animals. The correlation between repopulation rate and age suggests that the repopulation is thymus dependent and that the repopulated T cells are probably naive T cells. This reagent should be a valuable tool in studying the role of memory T cells in rhesus models of autoimmune diseases and protocols of tolerance induction after organ transplantation.

Animals↗
PubMed1996

Middle cerebral artery occlusion in Wistar and Fischer-344 rats: functional and morphological assessment of the model.

Cerebral infarction volume after occlusion of a short proximal segment of the middle cerebral artery (MCA) is reported to be different in Wistar compared to Fischer-344 (F344) rats, in both size and variability. Knowledge about the cause of these differences might enable us to explain and perhaps reduce the variation in infarct volume and create a reproducible model of focal cerebral ischemia in the rat. We investigated in Wistar and F344 rats both the effect of occlusion of a long proximal MCA segment on cerebral infarction volume, visualized by magnetic resonance imaging and histology, and the morphology of the major cerebral arteries. Occlusion of a long proximal MCA segment resulted in a striatal and a small cortical infarction in Wistar and a striatal and sizable cortical infarction in F344 rats (as is the case after occlusion of a short proximal MCA segment). In Wistar rats, however, occlusion of a long proximal MCA segment strongly reduced the variability in infarction volume in comparison to occlusion of a small proximal MCA segment. Analysis of the morphology of the major cerebral arteries showed a significantly higher number of proximal side branches of the long proximal MCA segment in Wistar rates than in F344 rats. We conclude that after short-segment proximal MCA occlusion, extreme variability in cerebral infarction volume in Wistar rats compared to F344 rats may be attributable to a significantly greater number of proximal MCA side branches in Wistar rats than in F344 rats.

Animals↗
PubMed1995

Identification of an Mhc-DPB1 allele involved in susceptibility to experimental autoimmune encephalomyelitis in rhesus macaques.

Experimental autoimmune encephalomyelitis (EAE) is an inducible autoimmune disorder that in rodents is known to be influenced by genetic background, specifically the Mhc class II region. Immunization of a group of outbred rhesus macaques with bovine high homogenate results in induction of the disease in approximately 65% of the animals. No clear association between the Mamu-DR or -DQ subregion of the rhesus macaque MHC (MhcMamu) and susceptibility or resistance to the disease has been documented. In this communication we describe a CD4+ Th cell line, isolated from an animal diagnosed with EAE, which proliferated in response to purified bovine myelin basic protein (MBP), a major constituent of the myelin sheath surrounding nerve cells. More specifically it only recognized a peptide including residues 61-82 of the molecule. Analysis of the T cell receptor (Tcr) usage of this MBP reactive T cell line showed functional transcripts for only two members of the V alpha 1 and one of each of the V beta 3 and V beta 6 families. The antigen-specific proliferative response was inhibited by a mAb reactive with MHC-DP molecules. Molecular analysis of the Mamu-DP region, in concert with allogeneic antigen presentation studies, demonstrated that the Mamu-DPB1*01 gene product functions as the restriction element for MBP peptide presentation. Retrospective analyses showed that this particular allele is frequently found in the group of EAE susceptible animals but is absent in the resistant animals (P < 0.01). As a consequence, the Mamu-DPB1*01 allele may represent one of the risk factors involved in determining susceptibility to EAE in an outbred population of rhesus macaques.

Alleles↗
PubMed1995

Characterization of the natural immune response of rhesus monkey CD4+ve T cells to the bacterial antigen streptolysin O (SLO).

Rhesus monkeys show a high proliferative T cell response to the bacterial exotoxin SLO without prior immunization. The present study was undertaken to characterize this naturally present SLO-responsiveness with particular emphasis on CD4+ve reactive T cells. It is demonstrated that the frequency of SLO-reactive cells in the circulation.ranges between 1 in 75 and 1 in 610 CD4+ve T cells as determined with limiting dilution analysis. It is also shown that induction of a good proliferative response requires Mhc-DR matching between T cell and the antigen presenting cells (APC). Stable and DR-restricted SLO-specific CD4+ve T cell lines were generated from CD8 depleted peripheral blood mononuclear cells (PBMC). The SLO-reactive CD4+ve cell lines are tentatively characterized as Th1-like based on the predominant production of interferon-gamma (IFN-gamma) over IL-4, although this seems contradicted by the IL-4 dependent growth of the lines.

Animals↗
PubMed1995

Therapy with OKT3 monoclonal antibody in refractory T cell acute lymphoblastic leukemia induces interleukin-2 responsiveness.

Administration of cytokines to patients with leukemia or lymphoma may recruit dormant malignant cells into cell cycle and thus make them more susceptible to chemotherapy. We treated a patient with refractory T cell acute lymphoblastic leukemia (ALL) with OKT3 monoclonal antibody and observed a dramatic but transient decrease of lymphoblasts. The T ALL cells were rather mature by morphology and immunophenotyping, expressing CD7, CD4, CD8 and CD3 surface antigens and nuclear TdT. Cytogenetic analysis revealed inversion of chromosome 14(q11q32.1). A total of 500 mg OKT3 (maximum dose 50 mg/day) was given. A decrease of lymphoblasts in the blood and a reduction of spleen size was observed. Complement levels dropped remarkably. Despite increasing serum levels of tumor necrosis factor, treatment was well tolerated overall. CD3 therapy induced strong IL-2 responsiveness of the lymphoblasts. Thus, OKT3 antibody treatment not only significantly decreased CD3-positive tumor cells, but also induced IL-2-mediated proliferation. This may also allow sequential application of CD3 and IL-2 to render certain T cell tumors more susceptible to chemotherapy.

Adult↗
PubMed1994

An ear swelling reaction for in vivo monitoring of inflammatory T cell activity in collagen-arthritic rats.

T cells play a dominant role in the pathogenesis of collagen-induced arthritis (CIA). The effector mechanism involves a delayed-type hypersensitivity reaction in the synovial joint. Here we describe a new test system, named a flare reaction, to monitor directly this inflammatory T cell function. It is shown that type II collagen (CII) injected into the pinna of the ear is a target for CII-reactive inflammatory T cells formed during the early pathogenesis of CIA. The inflammatory swelling of the joint and the CII-injected ear in CIA rats develop in a coordinated manner. This assay greatly facilitates monitoring of in vivo activated inflammatory T cells during the induction of CIA.

Animals↗
PubMed1994

Major histocompatibility complex class I-associated vaccine protection from simian immunodeficiency virus-infected peripheral blood cells.

To evaluate the effectiveness of vaccine protection from infected cells from another individual of the same species, vaccinated rhesus macaques (Macaca mulatta) were challenged with peripheral blood mononuclear cells from another animal diagnosed with acquired immune deficiency syndrome (AIDS). Half of the simian immunodeficiency virus (SIV)-vaccinated animals challenged were protected, whereas unprotected vaccinates progressed as rapidly to AIDS. Protection was unrelated to either total antibody titers to human cells, used in the production of the vaccine, to HLA antibodies or to virus neutralizing activity. However, analysis of the serotype of each animal revealed that all animals protected against cell-associated virus challenge were those which were SIV vaccinated and which shared a particular major histocompatibility complex (MHC) class I allele (Mamu-A26) with the donor of the infected cells. Cytotoxic T lymphocytes (CTL) specific for SIV envelope protein were detected in three of four protected animals vs. one of four unprotected animals, suggesting a possible role of MHC class I-restricted CTL in protection from infected blood cells. These findings have possible implications for the design of vaccines for intracellular pathogens such as human immunodeficiency virus (HIV).

Amino Acid Sequence↗
PubMed1994

Expansion and contraction of rhesus macaque DRB regions by duplication and deletion.

Previous sequence analysis of the rhesus macaque MHC (MhcMamu) class II DRB region has allowed the detection of at least 34 alleles belonging to different lineages. In this communication, 36 new Mamu-DRB alleles are reported. The gene content of the DRB region has been determined for several homozygous animals of consanguineous origin. As in other primates, the number of DRB genes present per haplotype is not constant, varying from two to six genes in rhesus macaques. Six major groups of DRB haplotypes have been defined in our rhesus macaque colony. Two haplotype groups were found to carry, as well as other Mamu-DRB genes, two genes that cluster into distinct HLA-DRB1 lineages. In one of these two groups, a haplotype harbors another two sets of DRB alleles that belong to the Mhc-DRB6 and -DRB*W6 lineages, respectively. Such a haplotype was probably generated by duplication, and our data suggest that after this particular expansion of the DR region, one of the duplicated Mamu-DRB6 alleles was the target of an Alu insertion. Although certain transspecies allelic lineages are evolutionarily stable, and have been conserved for at least 36 million years, the rhesus macaque class II haplotypes differ significantly from those found in humans, chimpanzees, and gorillas. Mhc-DRB regions are therefore comparatively unstable over longer evolutionary time spans, with regard to both the number of genes and the gene content, and must have been subjected to expansion and contraction.

Alleles↗