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Biomedical subjects

M Jonker

Publications and source records attributed to M Jonker.

118 records · Page 7Linked to original sources

Influence of previous immunization on skin graft survival.

The results of skin grafts transplanted in immunized and nonimmunized recipients was analysed. Specific sensitization for HLA-A or B determinants shortens graft survival if the recipients were immunized by s.c. injections of leukocytes. When the recipients had been pregnant, no such influence of specific HLA-A or B sensitization could be demonstrated. The variance in mean survival times of grafts exchanged between mixed lymphocyte culture (MLC)-positive donor-recipient combinations was significantly smaller than the variance in mean survival time (MST) of grafts exchanged between MLC-negative combinations. This difference could be the result of the influence of allograft immune-activating determinants of different strength in the MLC-negative donor-recipient combinations. Also the variance in MST of grafts in immunized recipients was significantly larger than the variance in MST of grafts in nonimmunized recipients. Apart from the obvious effect of HLA-A and B sensitization, other less well documented factors must have influenced graft survival. We did not find evidence for a graft enhancing effect of B cell-specific antibodies.

Antibodies↗

Inhibition of MLC stimulator function by antibodies directed to non-HLA antigens.

The properties of five human alloantisera which inhibit the stimulating capacity of cells in an MLC reactions are described. All of the sera showed patterns of inhibition in families which did not correlate with HLA haplotypes. In a large proportion of the families investigated the sera did not react with parental cells but inhibited the cells from one or more of the children. Absorptions were performed with one of these sera using such non-reactive parental cells. Paternal cells absorbed out the inhibiting activity while maternal cells did not. This indicates that expression of the antigen with which the inhibiting antiserum reacts is insufficient for inhibition and other factors, either environmental or inherited from the mother, influence the capacity of the antiserum to cause inhibition. This antigen was most likely a non-HLA antigen.

Absorption↗

Can anti HLA-A and -B antibodies inhibit the MLC test?

Eleven lymphocytotoxic pregnancy sera were tested for inhibition in the MLC test. Responder inhibition and stimulator inhibition were analyzed separately by using cells from the serum producer as stimulator and responder respectively. Only three sera showed inhibitionof responder function, whereas all sera showed inhibition of stimulator function. The specificity of the latter inhibition was at least in part attributable to antibodies directed to specificities other than B-cell specificities (presumed to be coded for in the HLA-D region). This was deduced from the fact that platelet eluates devoid of anti B-cell antibodies effectively inhibited in MLC.

Antibody Specificity↗

Inhibition of the mixed leukocyte reaction by alloantisera in man. I. Technical aspects.

Some technical aspects of MLC inhibition by sera obtained from multiparous women were studied. The variability of the MLC response was very high. The serum source used in the cultures was probably to a large extent responsible for this variability. Aspecific inhibition, which was observed with some test sera, could be removed by dialysis against PBS. To make the evaluation of inhibition by immune sera objective, a scoring system was introduced for the degree of inhibition. Test sera were usually added to the cultures. Alternatively, stimulator and responder cells were preincubated with the test serum. Preincubation of the stimulator cells did not show a difference in inhibition pattern when this was compared with serum addition. Preincubation of the responder cells showed a completely different inhibition pattern. The MLC inhibition test compared very well with an indirect immunofluorescence test and a cytotoxicity test using B-cell enriched cell suspensions.

Cytotoxicity Tests, Immunologic↗

Inhibition of the mixed leukocyte reaction by alloantisera in man. II. Incidence and characteristics of MLC-inhibiting antisera from multiparous women.

The incidence of MLC-inhibiting antibodies was determined in 42 pregnancy sera. MLC's were carried out between the cells from the serum donor and her husband in the presence of nonimmune AB serum and the test serum. Fifty per cent of the sera reduced the MLC response to less than 40% of the control values. Only four sera had lymphocytotoxic activity. The inhibition was strong against the specific immunizor, less strong against random unrelated cells and weak against cells which were SD-identical with the serum donor. Absorptions with lymphocytes and platelets were carried out. Lymphocytes removed activity in three of the four sera tested. Platelets removed activity from one serum. It was concluded that both anti-LD and anti-SD antibodies were able to inhibit the MLR at the stimulator cell level.

Cytotoxicity Tests, Immunologic↗

Successful suppression of the early rejection of pig islets in monkeys.

Primary nonfunction (PNF) is seen very frequently after xenogeneic transplantation of islets of Langerhans. In a pig-to-rat model we recently observed that no PNF occurs when the islets are kept in culture at 37 degrees C for 1-2 weeks prior to transplantation. In order to investigate the rejection mechanisms in a preclinical model, we transplanted cultured porcine islets under the capsule of both kidneys in four cynomolgous monkeys. Islets were isolated from adult sows by means of digestion with Liberase in University of Wisconsin solution (UWS). The digest was purified by a density gradient of OptiPrep in UWS. Highly purified (>95%) islets were cultured 1-2 weeks in RPMI. All monkeys showed significant titers of preformed anti-pig antibodies. The immunosuppression of the monkeys consisted of cyclophosphamide (Cy) (2 days), cyclosporin A (CsA), and prednisolone. Anticipating a fast rejection we carried out nephrectomies at different time points within 2 weeks after transplantation. Following unilateral nephrectomy, well-preserved islets with no signs of rejection were observed between 3 and 7 days posttransplant. Later, between days 11 and 15 posttransplant, histology in the first three animals demonstrated no islets. In the fourth monkey histology on day 11 showed islets with excellent morphology and some small focal infiltrates. The highest CsA blood levels (around 1000 ng/ml) were found in animals with the best graft survival. We conclude that cultured porcine islets can be grafted without hyperacute rejection in monkeys with preformed anti-pig antibodies. In the presence of high levels of CsA only marginal signs of a cellular immune response were observed 11 days after transplantation.

Animals↗