[Acquired immunological defects in homosexual men. A new disease entity].
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Biomedical subjects
Publications and source records attributed to E Dickmeiss.
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Lymphocytes from dinitrochlorobenzene-sensitized individuals can be stimulated in vitro by autologous dinitrophenyl (DNP)-conjugated lymphocytes to produce cytotoxic T lymphocytes (CTLs). The activity of these CTLs is specific for DNP-conjugated target cells, and there is no cross-reaction with nitrosodimethylaniline- or trinitrophenyl-conjugated target cell. Evidence is presented which makes it improbable that the cytotoxicity is caused by an antibody-dependent (ADCC-like) mechanism. Most of the DNP-specific cytotoxicity is restricted by the HLA-ABC antigens of th CTL donor, and there is only a low degree of lysis of DNP-conjugated allogeneic target cells not sharing HLA-ABC antigens with the donor. The CTLs did not lyle non-conjugated allogeneic target cells. When CTLs were tested against allogeneic DNP-conjugated targets sharing only one of the HLA-ABC antigens of the CLT donor, it was seen that the phenomenon of preferential restriction was pronounced; that is, only some of the antigens of the donor were restricting. A certain pattern has emerged: some antigens (e.g. A2) are good restricting antigens, some (e.g. B12) do not restrict, and some (e.g. B5) function well in one donor but not in another. The serologically cross-reacting antigens A2 and A28 did not restrict mutually. HLA-C antigens may in some donors function as restricting antigens.
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The immunological in vitro responses of cadaver kidney transplanted patients against donor specific target cells were investigated with the test systems for antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cell-mediated cytotoxicity (DCMC). The test systems were used in 58 recipients just before the transplantation. Nine recipients (17%) had positive donor directed ADCC reactivity and of these seven had early rejection episodes, but this outcome was not significantly different from the outcome in the ADCC negative group. Only one recipient showed positive donor directed DCMC reactivity and had early loss of the graft in rejection. The test systems were further used to monitor the donor specific responces after the transplantation in 32 recipients. Positive DCMC reactivities were significantly correlated with clinical rejections but most often positive reactions occurred too late to be of predictive value. The donor specific ADCC reactivity after transplantation was not clearly correlated with rejections. It is concluded that the predictive and diagnostic values of the two test systems were too weak to justify their use as routine methods in the clinical management of the kidney transplanted patient.
An individual, BK, repeatedly gave typing responses against homozygous typing cells representing more than two HLA--D antigens. Family studies showed that she had inherited the HLA--Dw2 and Dw7 determinants, in agreement with results from primed lymphocyte typing. The HLA--A, B, C types of the stimulators giving rise to unexpected typing responses all involved the HLA--A1, A3 or A11 antigens. The hypothesis of this specificity in low-responsiveness was confirmed in the independent stimulator sample provided by the 7th workshop homozygous typing cell panel. The same pattern was observed when BK was tested as a responder towards related and unrelated heterozygous stimulators. Furthermore, in three-cell experiments it was found that BK cells were able to suppress the response to the Dw-identical individual, BS, towards stimulators carrying HLA--A1, A3, or A11. This effect of BK's cells appeared to be radiosensitive. We were not able to demonstrate suppressive supernatant factors in the relevant cultures, neither were we able to find circulating cytotoxic cells by the direct CML-technique, nor an accelerated cytotoxic response by the indirect CML-technique against targets carrying HLA--A1 or A3. This is the first demonstration of induction of suppressor cells in MLC by HLA--A, B, C antigens in the stimulator cells.
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A pair of dizygotic twins of opposite sex were incidentally found to be erythrocyte chimeras. The chimerism was found to include the lymphocyte population as well, since the twins differed for the maternal while sharing one paternal HLA haplotype. In addition to lymphocytes carrying antigens controlled by the inherited maternal haplotype, each of the twins had a small fraction--about 15%--of lymphocytes of the other twin's type. Both twins are healthy and have normal children. Investigations of the family by mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) tests showed that the two haplotypes by which the twins differed carried different HLA-D determinants; even so the lymphocytes of each twin were completely nonresponsive in MLC and CML to those of the other twin. No 'blocking' factors could be demonstrated in the serum of the twins. These results support Burnet's theory of clonal selection in fetal life.
One-way mixed lymphocyte culture reactivity of recipient lymphocytes against the donor lymphocytes was measured in 11 recipients of cadaver kidneys. Peripheral blood was drawn from donors and recipients before the transplantation and lymphocytes isolated and frozen down for later typing. In one experiment, the lymphocytes from 11 recipient-donor pairs were thawed and the reactivity of the lymphocytes of the recipient towards the irradiated lymphocytes of the donor was estimated. Two unrelated controls were included, and the results were expressed as stabilized relative response taking into account both variations in responder- and stimulator capability of the lymphocytes. Four patients with a high relative response (above 50) had rejection episodes during the first month of transplantation in contrast to seven patients with a low relative response, who had no rejection episodes during the first month (p = 0.003). At six months, three of the four high responders had lost their graft compared to two of the seven low responders.
The test systems for antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cell-mediated lympholysis (DCML) were used to measure the immunological response of kidney transplanted patients against donor related targets before and after transplantation and in long term allograft recipients. An isolated positive ADCC cross march was found to indicate a grave graft prognosis. Positive DCML reactions were correlated to clinical rejection. In long term recipients antibodies reactive in ADCC against donor related targets seemed to be correlated with a state of chronic rejection.
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The graft-directed, cell-mediated immunity in kidney-allografted patients was examined with a seriologically defined (SD), donor-unrelated panel of antigenic material in clinical steady state, soon after transplantation, and during acute rejection episodes. The SD antigens were selected from the panel on the basis of predictions hypothesized from the SD match of donor and recipient. The cell-mediated immunity was measured by the direct leukocyte migration agarose test (LMAT). Positive reactions in kidney-transplanted patients were induced particularly by one preparation (antigen 52) and were unpredictable on the basis of SD classification. The investigation shows that other antigenic determinants, different from SD antigens, probably play an important role as inducers of cell-mediated, graft-associated immunity in kidney-transplanted patients.
Twenty-two patients on chronic hemodialysis were tested for direct lymphocyte-mediated cytotoxicity (DCML) and antibody-dependent lymphocyte-mediated cytotoxicity (LALI) against selected panels of normal donor lymphocytes. The DCML reaction was only positive in patients who had received blood transfusions within the two or three months prior to testing. Thus this reaction has limited value in practice as a parameter for presensitization. The use of third-party effector cells and of target cells precoated with antibody in the LALI reaction was evaluated, and it is advocated that effector cells from the patient investigated and direct application of patient serum to reaction mixtures should be preferred in order to avoid false negative reactions. In patients who had once manifested lymphocytotoxins, LALI disclosed a much broader reactivity than seen with a conventional complement-dependent cytotoxicity technique (CDC), whereas in this study patients who had never developed cytotoxins were also negative with the LALI technique. It is concluded that a positive LALI cross-match, in spite of a negative CDC cross-match, will be a common finding in donor-recipient combinations where the recipient has preformed cytotoxins. The effect of this on subsequent graft prognosis needs further clarification.
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We studied the distribution of HLA-DP antigens in 74 HIV-infected Danish homosexual men and 188 ethnically matched healthy individuals, using the primed lymphocyte typing (PLT) technique. Forty of the patients developed AIDS within 3 years after diagnosis, whereas the remaining 34 were healthy or had only minor symptoms for 3 years or more (median observation time was 42 months). HLA-DPwl seemed to be decreased (relative risk = 0.3) in AIDS patients (5.0 per cent) when compared to patients with minor symptoms (14.7 per cent) and healthy controls (14.9 per cent). These differences were, however, not statistically significant. There were no other apparent deviations between patients (or subgroups of patients) and controls.