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Biomedical subjects

M Jonker

Publications and source records attributed to M Jonker.

At least 55 records · Page 3Linked to original sources
PubMed1994

Gel electrophoretic analysis of rhesus macaque major histocompatibility complex class II DR molecules.

Rhesus macaque MHC class II DR molecules were isolated from radiolabeled B-cell line extracts by immunoprecipitation with the mAbs 7.3.19.1 and B8.11.2 and subsequently analyzed by 2D-gel electrophoresis. The B-cell lines used for this study were obtained from monkeys that are homozygous for the Mamu-DR region as defined by serologic techniques. Some of these animals have been selectively bred and originate from consanguineous matings. These analyses show that monkeys with the same allotyping may express different types of DR molecules. As in humans, the number of DR molecules expressed per haplotype is not constant and varies from 1 to 3, depending on the serologically defined Mamu-DR specificity, whereas it has been shown that the number of Mamu-DRB genes present per haplotype varies from 2 to 6. Therefore the present study also demonstrates that some of the rhesus macaque DR regions contain one or more pseudogenes.

Animals↗
PubMed1993

Resistance to collagen-induced arthritis in rats and rhesus monkeys after immunization with attenuated type II collagen.

Immunization of susceptible rodent or primate species with type II collagen (b-CII) from bovine origin induces type II collagen-induced arthritis (CIA). The disease is characterized as a systemic polyarthritis associated with humoral and cellular autoimmunity to CII and shares similarity with human arthritic diseases. The objective of this study was to develop a procedure for induction of resistance to CIA in animals, which possess a certain major histocompatibility complex phenotype that makes them prone to develop CIA (susceptible). It is shown that by immunization with an attenuated form of CII, in which arthritogenic epitopes have been destroyed by heat denaturation, disease resistance is induced in a susceptible inbred rat strain (RT-1u) and in an outbred population of susceptible rhesus monkeys (lacking the Mamu-A26 allele). In both species the disease resistance is connected with modulation of anti-CII autoantibodies of the IgM isotype. This protocol may provide a basis for effective and safe methods to induce protection to autoimmune arthritis in those subjects that are genetically prone to develop such a disease.

Animals↗
PubMed1993

Induction of an anti-vaccine response by T cell vaccination in non-human primates and humans.

Experimental and spontaneous autoimmune disease in animals can effectively be prevented and treated by application of pathogenic autoreactive T cells in an attenuated form. This approach has become known as T cell vaccination. T cell vaccination exploits specifically the ability of the immune system to regulate its autoreactive T cells by mechanisms of network control. The success of T cell vaccination in a variety of rodent animal models has raised hopes for its use as an effective and specific therapy in human autoimmune disease. The aim of this study was to induce an anti-T cell response by T cell vaccination in humans and primates as a pre-clinical study into the feasibility and toxicity of T cell vaccination. Using bulk cultures of T cells from the peripheral blood or an inflamed joint, it was possible to induce a T cell response specific for the injected vaccine and its activation state both in rhesus monkeys and in two patients with active rheumatoid arthritis. In one of the patients there was already a spontaneous T cell response against a mitogen driven T cell line from the peripheral blood, but not against a control T cell line specific for tetanus toxoid, suggesting that regulatory T cell networks are operative in patients with autoimmune disease. Significant clinical effects or side-effects were not observed. The results suggest that T cell vaccination in humans is feasible and non-toxic. It is likely to influence an already ongoing regulatory process. Conditions for making T cell vaccination an effective therapy need still to be worked out by further studies both in primates and in less complex human immune processes.

Animals↗
PubMed1993

Mhc-DRB and -DQA1 nucleotide sequences of three lowland gorillas. Implications for the evolution of primate Mhc class II haplotypes.

Mhc-DRB and -DQA1 second-exon and -DRB 3'-untranslated-region nucleotide sequences of three lowland gorillas with no known family relationship with each other and of two HLA homozygous typing cell lines were determined and compared with published primate Mhc-DRB and -DQA1 sequences. Eleven distinct MhcGogo-DRB second-exon sequences were found, which represent the gorilla counterparts of the HLA-DRB1*03, -DRB1*10, -DRB3, -DRB5, and -DRB6 allelic lineages. One Gogo-DRB second-exon sequence does not have an obvious human counterpart and is tentatively designated Gogo-DRBY*01. The gorilla equivalents of the HLA-DRB2 and -DRB8 loci were identified as judged on Mhc-DRB 3'-untranslated-region sequences. In addition, four different Gogo-DQA1 alleles belonging to three different allelic lineages were detected. The Mhc-DRB-DQA1 haplotypes of these gorillas were deduced based on the obtained Mhc-DRB and -DQA1 sequences and the two published Mhc-DRB haplotypes of the lowland gorilla Sylvia. All deduced Gogo-DRB-DQA1 haplotypes show gene constellations different from known HLA-DRB-DQA1 haplotypes, while some of the Gogo-DRB haplotypes presented here contain more DRB genes than the HLA-DRB haplotypes. Based on phylogenetic trees, bootstrap analyses, and the gorilla, chimpanzee, and human Mhc-DRB haplotypes described, we propose that at least two Mhc-DRB loci, here tentatively designated Mhc-DRBI and -DRBII, existed on an ancient primate Mhc-DRB haplotype. The Mhc-DRB1*01, -DRB1*02 (-DRB1*15 and -DRB1*16), -DRB1*03 (-DRB1*03, -DRB1*08, -DRB1*11, -DRB1*12, -DRB1*13, and DRB1*14), and -DRB1*10 allelic lineages and -DRB3 and -DRBY loci probably evolved from the hypothetical primate Mhc-DRBI locus, whereas the present primate Mhc-DRB2, -DRB4, and -DRB6 loci originate from the ancient Mhc-DRBII locus of this core primate Mhc-DRB haplotype.

Amino Acid Sequence↗
PubMed1993

In vivo treatment with a monoclonal chimeric anti-CD4 antibody results in prolonged depletion of circulating CD4+ cells in chimpanzees.

Chimeric M-T412 (cM-T412), an anti-CD4 antibody, was tolerated in chimpanzees at a dosage of 5 mg/kg per day for up to 7 consecutive days, or 5 mg/kg per dose, twice weekly for 4 weeks. All cM-T412-treated chimpanzees showed a prolonged CD4-cell depression. Weak chimpanzee antibody responses to chimeric M-T412 were observed. One of the chimpanzees on the biweekly dosage regimen exhibited a hypersensitivity reaction immediately after receiving its seventh dose. Following supportive treatment, the animal recovered and remained asymptomatic during the non-treatment observation period. The hypersensitivity reaction was not an unexpected response considering the animal received repeated intermittent i.v. administration of a foreign protein. This animal also showed a chimpanzee antibody response to chimeric M-T412 after the seventh dose. Chimeric M-T412 also induced an anti-cM-T412 response in some of the other animals. The level of this response was lower than the anti-mouse responses observed in animals treated with murine anti-CD4. Moreover, the anti-cM-T412 response was mainly directed to idiotypic determinants. The decrease in CD4+ cells observed for all chimeric M-T412-treated chimpanzees is an expected effect of the anti-CD4 antibody. The duration of this CD4+ cell decrease is, however, much longer than observed for other CD4-specific MoAbs described. No selective loss of either memory or naive CD4+ cells was observed after either the single, 7-day or twice-weekly treatments. The CD4+ cell depression was reversible, although individual variation in time to recovery was observed. Therefore, cM-T412 could be a good candidate for clinical use in autoimmune conditions.

Animals↗
PubMed1993

The anti-arthritic and immunosuppressive effects of cyclosporin A on collagen-induced arthritis in the rhesus monkey.

The influence of cyclosporin A (CsA) on type II collagen-induced arthritis (CIA) in the rhesus monkey has been investigated. CsA was administered subcutaneously in a dose of 25 mg/kg per day during 9-18 days and additionally 12.5 mg/kg per day for 7 days. At this dosing regime no significant alterations of haematologic parameters were found, indicating that the toxicity of CsA was negligible. Administration of CsA after onset of arthritis had no beneficial effect, but when given between immunization and manifestation of clinical symptoms, CIA could be prevented completely. Moreover, these monkeys became resistant to the disease, because no arthritic activity could be observed upon a booster immunization with type II collagen (CII). The suppression of disease by CsA is reflected in reduced antibody levels to CII.

Animals↗
PubMed1993

Major histocompatibility complex class II DQ diversity in rhesus macaques.

By the use of restriction fragment length polymorphism analysis 10 Taq I fragments could be identified for the MhcMamu-DQA1 region. A strong correlation exists between the occurrence of Mamu-DQA1/Taq I fragments and Mamu-DQA1 allelic sequence variation. Most restriction fragments correspond with a unique Mamu-DQA1 allele, with one exception being the Taq I 4.5 kb fragment that is associated with two Mamu-DQA1 alleles. The RFLP technique allowed the identification of 15 Mamu-DQB1/Taq I restriction fragments, whereas sequence analysis has permitted the characterization of at least 20 different Mamu-DQB1 alleles. In this communication two unpublished Mamu-DQB1 sequences are described. For Mamu-DQB1, on only four occasions was it possible to demonstrate a correlation between a certain fragment and an allelic sequence. These analyses, performed on material from truly homozygous animals, allowed us to define which combinations of Mamu-DQA1 and -DQB1 molecules form heterodimers at the cell surface. In addition, these studies are helpful in typing non-human primate species that are used in biomedical research.

Alleles↗
PubMed1993

Major histocompatibility complex class II polymorphisms in humans and chimpanzees.

Allelic variation at the MhcPatr-DR and -DQ loci was studied by molecular biological techniques and compared to available HLA data. With regard to the number of allelic lineages, the chimpanzee shows a condensation of its major histocompatibility complex (MHC) class II repertoire as compared to humans. This does not have an impact on the overall degree of MHC class II polymorphism in the chimpanzee since a few lineages that are oligomorphic in humans display an extensive degree of polymorphism in the chimpanzee.

Alleles↗
PubMed1992

Mhc-DQB repertoire variation in hominoid and Old World primate species.

Comparison of 87 distinct Mhc-DQB sequences, obtained from 13 primate species, demonstrates that five out of eight trans-species Mhc-DQB allele lineages are at least 30 million years old and predate divergence of hominoid and Old World primate species. One lineage may be much older because its members are not only traced back in higher primates, but also are present in a New World primate species. Comparing Mhc-DQB repertoire variation in distinct species, allows one to pinpoint when certain polymorphisms were lost or gained in primate evolution. Heterogeneity observed among members of trans-species Mhc-DQB allele lineages can be explained in major part by point mutations, whereas intraexonic crossing-over is a potent mechanism in generating new allele lineages. The stability of Mhc-DQB polymorphisms is influenced by selective forces because distinct allele lineages appear to have accumulated nucleotide substitutions and amino acid replacements at different rates.

Alleles↗
PubMed1992

Resistance to collagen-induced arthritis in a nonhuman primate species maps to the major histocompatibility complex class I region.

Type II collagen-induced arthritis (CIA) is an experimentally inducible autoimmune disorder that is, just like several forms of human arthritis, influenced by a genetic background. Immunization of young rhesus monkeys (Macaca mulatta) with type II collagen (CII) induced CIA in about 70% of the animals. One major histocompatibility complex (MHC) class I allele was present only in young animals resistant to CIA and absent in arthritic animals. This strong association suggests that the MHC class I allele itself, or a closely linked gene, determines resistance to CIA. The mechanism controlling the resistance to CIA becomes less efficient in aged animals since older rhesus monkeys, which were positive for the resistance marker, developed a mild form of arthritis. At the cellular level it is demonstrated that resistance to CIA is reflected by a low responsiveness of T cells to CII. This association between a specified MHC class I allele and resistance to an autoimmune disease points at the importance of the MHC class I region in the regulation of the immune response to an autoantigen.

Alleles↗
PubMed1992

Lymphoproliferative disorders developing after transplantation and their relation to simian T-cell leukemia virus infection.

In this report the role of the HTLV-1-like simian T-cell leukemia virus (STLV) during the development of posttransplantation lymphoproliferative disorders (PTLPD) is described. To prevent rejection of an allogeneic transplant in 12 rhesus monkeys cyclosporin A (CyA), prednisone, and/or lymphocyte-specific monoclonal antibodies were used for immunosuppression. Seven monkeys died during the experiment between 22 and 179 days postoperatively. At autopsy in 4 monkeys PTLPD were found. In each case, STLV provirus was acquired during the experiment, either from the blood transfusions or allograft donors. Seroconversion of anti-STLV titers occurred in 3 monkeys. However, Southern blot analysis showed the presence of STLV provirus at the DNA level in all PTLP tissues. PTLPD morphology and phenotype varied significantly. In conclusion, for the first time the oncogenic potential of STLV is identified in a rhesus monkey transplantation model. Moreover, the importance of screening blood and organ donors for HTLV-1 must be emphasized.

Animals↗
PubMed1992

Evolutionary relationships among the primate Mhc-DQA1 and DQA2 alleles.

The variation of the Mhc-DQA1 and DQA2 loci of ten different primate species (hominoids and Old World monkeys) was studied in order to obtain an insight in the processes that generate polymorphism of major histocompatibility complex (Mhc) class II genes and to establish the evolutionary relationships of their alleles. To that end nucleotide sequences of 36 Mhc class II DQA1 and seven DQA2 second exons were determined and phylogenetic trees that illustrate their evolutionary relationships were constructed. We demonstrate the existence of four primate Mhc-DQA1 allele lineages, two of which probably existed before the separation of the ancestors of the hominoids and Old World monkeys (approximately 22-28 million years ago). Mhc-DQA2 sequences were found only in the hominoid species and showed little diversity. We found no evidence for a major contribution of recombinational events to the generation of allelic diversity of the primate Mhc-DQA1 locus. Instead, our data suggest that the primate Mhc-DQA1 and DQA2 loci are relatively stable entities that mutated primarily as a result of point mutations.

Alleles↗
PubMed1992

Mhc-DRB diversity of the chimpanzee (Pan troglodytes).

Fifty-four chimpanzee Patr-DRB and five human HLA-DRB second exons were cloned and sequenced from thirty-five chimpanzees and four human B-cell lines and compared with known Mhc-DRB sequences of these two species. Equivalents of the HLA-DRB1*02, -DRB1*03, -DRB1*07 allelic lineages and the HLA-DRB3, -DRB4, -DRB5, -DRB6, and -DRB7 loci were all found in the chimpanzee. In addition, two chimpanzee Patr-DRB lineages (Patr-DRBX and -DRBY) were found for which no human counterparts have been described. None of the Patr-DRB sequences is identical to known HLA-DRB sequences. The Patr-DRB1*0702 and HLA-DRB1*0701 alleles are the most similar sequences in a comparison between the two species and differ by only two nucleotides out of 246 sequenced. Equivalents of the HLA-DRB1*01, -DRB1*04, and -DRB1*09 alleles were not found in our sample of chimpanzees. A per locus comparison of the number of Patr-DRB alleles with the HLA-DRB alleles shows that the Patr-DRB3, -DRB4, -DRB5, and -DRB6 locus are, thus far, more polymorphic than their human homologs. The polymorphism of the Patr-DRB1 locus seems to be less extensive than that reported for the HLA-DRB1 locus. Nevertheless, the Patr-DRB1 locus seems to be the most polymorphic of the Patr-DRB loci. Phylogenetic analyses indicate that the HLA-DRB1*09 allele may have originated from a recombination between a Mhc-DRB5 allele and the DRB1 allele of a Mhc-DR7 haplotype. Although recombination seems to increase the diversity of the Patr-DRB alleles, its contribution to the generation of Patr-DRB variation is probably low. Hence, most Patr-DRB diversity presumably accumulated via recurrent point mutations. Finally, two distinct Patr-DRB haplotypes are deduced, one of which (the chimpanzee equivalent of the HLA-DR7 haplotype) is probably older than 6-8 million years.

Amino Acid Sequence↗
PubMed1992

Evolutionary stability of transspecies major histocompatibility complex class II DRB lineages in humans and rhesus monkeys.

Sequence analysis of rhesus monkey (Macaca mulatta) polymorphic second exon of major histocompatibility complex class II DRB subregion genes demonstrates the existence of at least 34 alleles. Some of these rhesus monkey alleles are very similar (or nearly identical) to HLA-DRB alleles. These data demonstrate that members of the lineages for Mhc-DRB1*03, -DRB1*04, -DRB1*10, and the loci of Mhc-DRB3, -DRB4, -DRB5, and -DRB6 predate speciation of man and rhesus monkey and were already present 25 million years ago. Calculation of evolutionary rates suggests that the various allele lineages have differential stabilities. Furthermore, the data indicate that distinct species may not have inherited or lost transspecies Mhc-DRB lineages in evolution, because several allele lineages in rhesus monkeys appear to be absent in humans and vice versa.

Alleles↗
PubMed1991

Collagen-induced arthritis in an outbred group of rhesus monkeys comprising responder and nonresponder animals. Relationship between the course of arthritis and collagen-specific immunity.

It is speculated that the autoimmune response to type II collagen (CII) is a driving force in the pathogenesis of human rheumatoid arthritis (RA). In this report, we describe the relationship between the induction of collagen arthritis and the CII-specific humoral, as well as cellular, immune response in rhesus monkeys. Ten of 14 monkeys immunized with bovine type II collagen (B-CII) developed polyarthritis. Susceptible animals showed a T cell response to B-CII; resistant animals did not. After the primary immunization, the humoral response to B-CII, as well as to rhesus monkey type II collagen, was dominated by antibodies of the IgM isotype in the susceptible animals and by antibodies of the IgG isotype in the resistant animals. Because of the close phylogenic relationship between the rhesus monkey and humans, these data contribute valuable information about the role of CII-specific immunity in the pathogenesis of human RA.

Animals↗
PubMed1991

Major histocompatibility complex ancestral haplotypes in the chimpanzee: identification using C4 allotyping.

In humans, certain major histocompatibility complex (MHC) supratypes mark unique DNA segments which have been conserved from a common but remote ancestor. In order to determine whether these ancestral haplotypes (AHs) exist in nonhuman primates, C4 allotyping was undertaken on 71 chimpanzees. Four large pedigrees were available. There are at least seven codominant C4 alleles at two loci. Null alleles are also present. It was possible to assign class I, class II, and C4 alleles to 37 unrelated haplotypes; several supratypes occurred two or more times. These putative AHs included some with alleles which resemble those carried by certain human AHs. These data provide evidence that similar MHC AHs are present in the chimpanzee and human. The present approach provides a basis for comparative studies examining the evolutionary and functional significance of the MHC.

Animals↗