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Biomedical subjects

M Jonker

Publications and source records attributed to M Jonker.

At least 73 records · Page 4Linked to original sources
PubMed1991

RFLP analysis of the rhesus monkey MHC class II DR subregion.

Restriction fragment length polymorphism (RFLP) analysis was performed on a panel of 39 serologically typed DR homozygous monkeys. DNA was digested with the restriction enzyme TaqI and hybridizations were carried out with a human leukocyte antigen (HLA)-DR beta 3'UT-specific probe. In addition a panel of 18 monkeys was analyzed comprising experimental autoimmune encephalomyelitis (EAE) susceptible and nonsusceptible animals. The number of DRB/TaqI fragments detected for the various DR specificities varied from two to six, suggesting that the number of DRB genes per haplotype is not constant. RFLP typing allows that most serologically defined DR specificities can be subdivided. This knowledge was applied to define the DR specificities of the animals used for EAE experiments.

Animals↗
PubMed1991

Autoimmunity in non-human primates: the role of major histocompatibility complex and T cells, and implications for therapy.

Two autoimmune disease models were studied in rhesus monkeys: type II collagen-induced arthritis (CIA) and experimental allergic encephalomyelitis (EAE). Unrelated outbred animals were used in these studies. In both models disease resistant and susceptible individuals could be identified. Susceptibility correlated with in vitro cellular responsiveness to antigen in the CIA model. In both models resistant as well as susceptible individuals developed a humoral response to the inducing antigen. However, there is an indication that IgM antibodies play a crucial role in the induction of CIA. No clear association between major histocompatibility complex (MHC) type and disease incidence was found although a higher frequency of a certain DR type was observed in EAE susceptible monkeys. It is likely that both the antigen binding capacity of the MHC class II molecules and the T-cell repertoire play an important role in determining whether disease will develop or not.

Animals↗
PubMed1991

Acquired resistance to type II collagen-induced arthritis in rhesus monkeys is reflected by a T cell low-responsiveness to the antigen.

Ten out of 14 rhesus monkeys developed arthritis after a single immunization with bovine type II collagen (B-CII). In contrast to primary resistant monkeys, arthritic animals showed a B-CII specific T cell proliferation during the induction phase of the disease. All surviving animals showed a full remission of the disease. Two monkeys acquired resistance to collagen-induced arthritis (CIA) after one period of disease, but in three animals a booster immunization with B-CII induced a slight flare-up. It is demonstrated that B-CII immunized rhesus monkeys have the capacity to restore resistance to CIA. The development of resistance to CIA is reflected by a decreased T cell responsiveness to B-CII. It is shown that the lack of IL-2 plays a role in B-CII-induced T cell low-responsiveness. A potential role of CD8+ T cells in the down regulation of the T cell response to B-CII is discussed.

Animals↗
PubMed1991

Monoclonal antibodies for immunohistochemical labeling of immunocompetent cells in frozen sections of rhesus monkey tissues.

Twenty-eight anti-human and two rhesus specific monoclonal antibodies (MAbs) were evaluated for immunohistochemical peroxidase staining reactivity in rhesus monkeys lymph nodes, thymus, liver, and skin allografts. Reactivity with the following antigens was assessed: MHC class I, II-DR, -DQ, and -DP antigens; leukocyte markers CD1, CD2, CD3, CD4, CD8, CD14, CD16, CD25, CD57; a proliferation associated nuclear antigen; interferon-gamma and tumor necrosis factor-alpha. Twenty-three MAbs proved to be suitable for immunohistochemical staining on frozen sections.

Animals↗
PubMed1990

Major histocompatibility complex class II-restricted antigen presentation across a species barrier: conservation of restriction determinants in evolution.

The existence of at least three alleles of the HLA-DRB3 gene within the human population is evident. These alleles express DRw52 determinants and react with monoclonal antibody (mAb) 7.3.19.1. The polymorphic epitope recognized by 7.3.19.1 is not only present on human cells but is also expressed on chimpanzee (Pan troglodytes) class II-positive cells. The 7.3.19.1 determinant already existed before speciation of man and chimpanzee, and is at least 5,000,000 yr old. Two-dimensional gel electrophoresis demonstrated that the various HLA- and Patr-DRw52 molecules that are reactive with 7.3.19.1 exhibit isoelectric point differences due to primary amino acid heterogeneity, as was confirmed by sequencing data. Sequence comparison allowed us to map the binding site of mAb 7.3.19.1 to the alpha helix of the major histocompatibility complex (MHC) class II DRB1 domain surrounding the antigen-binding cleft. Despite MHC sequence variation, chimpanzee antigen-presenting cells can present antigen (purified protein derivative) to human T cell lines and vice versa. Only the HLA- and Patr-DRw52 molecules were shown to function as restriction elements for antigen presentation across this species barrier. It is concluded that these particular restriction determinants probably have been conserved in evolution. The HLA- and Patr-DRw52 molecules represent alleles displaying polymorphism that has been selected for in evolution. Such "biomutants" may thus be more useful to study the biological significance of MHC molecules than MHC variants that have been generated by in vitro mutagenesis experiments.

Amino Acid Sequence↗
PubMed1990

The chimpanzee major histocompatibility complex class II DR subregion contains an unexpectedly high number of beta-chain genes.

The major histocompatibility complex (MHC) class II DR subregion of the chimpanzee was studied by restriction fragment length polymorphism (RFLP) analysis. Genomic DNA obtained from a panel of 94 chimpanzees was digested with the restriction enzyme Taq I and hybridized with an HLA-DR beta probe specific for the 3' untranslated (UT) region. Such a screening revealed the existence of 14 distinct DRB/Taq I gene-associated fragments allowing the definition of 11 haplotypes. Segregation studies proved that the number of chimpanzee class II DRB/Taq I fragments is not constant and varies from three to six depending on the haplotype. Comparison of these data with a human reference panel manifested that some MHC DRB/Taq I fragments are shared by man and chimpanzee. Moreover, the number of HLA-DRB/Taq I gene-associated fragments detected in a panel of homozygous typing cells varies from one to three and corresponds with the number of HLA-DRB genes present for most haplotypes. However, a discrepancy is observed for the HLA-DR4, -DR7, and -DR9 haplotypes since a fourth HLA-DRB pseudogene present within these haplotypes lacks its 3' UT region and thus is not detected with the probe used. These results suggest that chimpanzees have a higher maximum number of DRB genes per haplotype than man. As a consequence, some chimpanzee haplotypes must show a dissimilar organization of the MHC DR subregion compared to their human equivalents. The implications of these findings are discussed in the context of the trans-species theory of MHC polymorphism.

Animals↗
PubMed1990

Experimental immune mediated arthritis in rhesus monkeys. A model for human rheumatoid arthritis?

The induction of experimental arthritis in rhesus monkeys was studied by intradermal immunization of bovine type II collagen and antigens derived from Mycobacterium tuberculosis, Streptococcus pyogenes, and Eubacterium aerofaciens. The tested bacterial antigens proved to be not arthrogenic. Bovine type II collagen induced clinical arthritis in 50% of the rhesus monkeys. Type II collagen induced arthritis in rhesus monkeys proved to be a potential model to study clinical, serological, histological, genetic, and immunologic features associated with human RA.

Animals↗
PubMed1990

CD4 and CD8 T cells from SIV-infected macaques have defective signaling responses after perturbation of either CD3 or CD2 receptors.

Single-cell clones, designated E11S, C11R, and A1S, were obtained from the HuT-78 T cell line persistently infected with an isolate of Simian immunodeficiency virus (SIV), SIV/Mne. The infected clones, unlike uncloned uninfected HuT-78 cells, no longer expressed the CD4 marker and, after their CD3 receptors were cross-linked, had dramatically reduced intracellular free calcium ([Ca2+]i) responses. In one clone, E11S, the unresponsiveness was not limited to the inositol phospholipid pathway of signaling since a reduction in CD3-mediated activation of protein tyrosine kinase-dependent phosphorylation also was evident in this SIV-infected clone. These results led us to test whether T lymphocytes from animals infected with SIV had defective [Ca2+]i responses prior to detectable changes in CD4 levels or lymphadenopathy. The [Ca2+]i responses to both CD3 mAb and CD2 mAb were 10-50% less in T cells from Walter Reed stage 2 animals than in healthy controls. This anergy was more pronounced in chronically infected animals progressing to Walter Reed stage 3/4. The responses of these animals could not be augmented even when combinations of CD3 and CD4 mAb were used. Both CD4+CD44lo T cells, which are not infected with SIV, and the CD4+CD44hi T cell subset, previously shown to be the reservoir of SIV infection in blood, had pronounced defective responses to CD3 mAb. Similarly, both CD4+ and CD8+ T cells were consistently unresponsive in chronically infected animals, again implying that an indirect mechanism, rather than SIV infection per se, may be responsible for this immune dysfunction.

Animals↗
PubMed1990

The course of untreated acute rejection and effect of repeated anti-CD3 monoclonal antibody treatment in rhesus monkey liver transplantation.

The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN18) was studied in a rhesus monkey model. Eight RhLA-mismatched monkeys received initial postoperative immunosuppression with CsA/prednisolone for 28 days. After cessation, acute rejection occurred in all animals (days 28-50). Control animals (n = 3) receiving no rejection treatment developed a chronic progressive rejection and died at days 112-160. In the animals treated with FN18 (n = 5), the first acute rejection was successfully reversed. T lymphocytes were cleared from the peripheral blood and the graft. Increased class I and class II MHC-antigens on hepatocytes were reduced to normal levels within 5 days of treatment. The second rejection treatment remained ineffective in two animals with antiidiotypic antibodies to FN18 but was successful in two animals with a low antimouse response. These four animals survived 160-509 days. The results have a number of implications regarding the course of untreated rejection in human liver transplant recipients and repetitive rejection treatment with monoclonal antibodies.

Animals↗
PubMed1990

Synergistic immunosuppressive effects of monoclonal antibodies specific for interferon-gamma and tumor necrosis factor alpha. A skin transplantation study in the rhesus monkey.

Interferon gamma and tumor necrosis factor alpha play a significant role in the upregulation of host immunity and inflammation, for example by induction and enhancement of the expression of major histocompatibility complex class I and II antigens on a wide variety of cell types, both in vitro and in vivo. In this study two crossreactive monoclonal antibodies, one specific for human IFN-gamma (MD1), the other specific for human TNF-alpha (61E71), were tested for immunosuppressive potencies in a skin transplantation study in the rhesus monkey. Treatment with either MD1 or 61E71 alone did not prolong skin-graft-survival times. In combination, however, these antibodies augmented graft survival times significantly. Infiltration of the skin grafts by lymphocytes and histiocytes was delayed, and upregulation of MHC class I and II expression was retarded. This is the first reported demonstration of a synergistic effect of mAbs specific for IFN-gamma and TNF-alpha in the suppression of allograft rejection in primates.

Animals↗
PubMed1990

The importance of non-human primates for preclinical testing of immunosuppressive monoclonal antibodies.

Monoclonal antibodies (MAb) specific for lymphocyte markers can be considered as very specific immunomodulating drugs for treatment of allograft rejection and autoimmune diseases. Although the selection of potentially useful specificities of MAb can be made in rodents, human specific MAb can only be evaluated in man or a closely related species in which these human specific MAb are equally reactive. Because of the restricted reactivity of human specific MAb, non-human primates are the only available species for efficacy and safety studies. This article illustrates the usefulness of such studies in rhesus monkeys and chimpanzees for the testing of T cell specific MAb and other MAb interfering with the immune response in transplantation and autoimmunity.

Animals↗
PubMed1990

Human monoclonal antibody Ha6D3, a candidate for treatment of leukaemia? In vitro reactivity of Ha6D3 with leukaemic cells and in vivo applications in a chimpanzee.

The human monoclonal antibody Ha6D3 of the IgM type was used to stain malignant lymphoma cells from peripheral blood in flow cytometry and from cryosections of lymph nodes using the immunoperoxidase technique. It was found to react with peripheral white blood cells of all 12 cases of leukaemia and with lymph node cells of seven out of 11 B cell lymphomas and with the one T cell lymphoma tested so far. For in vivo experiments a batch of 70 mg Ha6D3 was purified and 6 mg Ha6D3 was injected intravenously into a chimpanzee with time intervals of 10 months and 1 month. The side effects observed were shivering, some muscular spasms and variations in the heart frequency. A decrease of lymphocytes of more than 50% was documented by haematogram analysis. The flow cytometry data showed that the Ha6D3 antigen does not modulate. Even after three repeated injections applied in a time interval of several months no immune response to Ha6D3 could be detected in vivo or in vitro. Based on these data we suggest that Ha6D3 may become a candidate for the treatment of certain leukaemias in vivo.

Animals↗