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Biomedical subjects

C Herwartz

Publications and source records attributed to C Herwartz.

10 recordsLinked to original sources
PubMed2000

Equal distribution of congenital blood cell chimerism in dizygotic triplets after in-vitro fertilization.

The special situation of multiple pregnancies following IVF has led to a growing interest in the assessment of embryonal development by means of molecular genetics. We report a case of congenital blood chimerism in dizygotic triplets (two boys, one girl) present in erythrocytes and leukocytes in both sexes. Routine pre-operative blood serology of the 6 year old female triplet revealed chimerism of the red cells. Flow cytometry of the erythrocytes and DNA analysis of the leukocytes demonstrated that all three children had the same proportions of male and female cells. Fluorescent in-situ hybridization (FISH) analyses revealed Y chromosomes in 84% of the girl's leukocytes and in 89/92% of the two boys' leukocytes. The true genetic lines were determined by analysing polymorphism of serum groups (glycoprotein, transferrin, protease inhibitor and plasminogen) secreted by non-haematopoetic tissue, by blood group typing of hair roots and by DNA analysis of endothelial cells. Evidently placental anastomoses allowed a reciprocal intra-uterine transfusion of blood stem cells in the triplets.

Blood Group Antigens↗
PubMed1997

Lack of in vitro synergy of clinically used antibodies specific for ICAM-1 and LFA-1.

Antibodies blocking adhesion molecules such as leucocyte function antigen (LFA)-1 (CD11a) and intercellular adhesion molecule (ICAM)-1 (CD54) are currently under clinical investigation for rejection prophylaxis in organ transplantation. In a murine model a combined though not a single application of antibodies against LFA-1 and ICAM-1 can induce tolerance towards heart transplants. No information regarding a possible synergistic action in man is as yet available. To fill this blank we tested the immunosuppressive capacity of ANTILFA (alpha-LFA-1)- and BIRR1 (alpha-ICAM-1) on human cells in vitro alone and in combination. Allogeneic venous endothelial cells, the lymphoblastoid cell line MSAB or peripheral blood mononuclear cells were used as stimulation. DNA synthesis, IL-2 production and cytotoxic T cell lysis were measured to assess T cell response. The strongest antibody effects were seen when endothelial cells were used as stimulators with the T cell response being assessed by IL-2 production. Most assays showed a similar immunosuppressive effect of LFA-1 and ICAM-1 blocking while the combination of both antibodies was not significantly more effective than each antibody alone. Thus our data do not provide a rationale for clinical trials using a combination of these antibodies.

Antibodies, Blocking↗
PubMed1995

Leukemia-specific allogeneic donor T cells: quantification by limiting dilution assay.

Allogeneic T cells are capable of discriminating between leukemia cells and non-malignant hematopoetic cells. This has been concluded from clinical BMT data and demonstrated by in vitro experiments. We analyzed the frequency and specificity of leukemia-reactive T cells from syngeneic and allogeneic blood donors by limiting dilution assays for interleukin-2-producing (TH1) and cytotoxic (CTLp) T cells. Target cells were leukemia blasts obtained from a patient with common ALL. Control targets were generated by EBV transformation. Effector cells were generated from the peripheral blood of the patient in remission, from his syngeneic brother and from eight healthy, HLA-mismatched volunteers. The effector cells were stimulated with leukemia cells and interleukin-2. Neither the patient nor his brother were able to generate anti-leukemic CTLp or TH1. The HLA-mismatched allogeneic donors displayed anti-leukemic CTLp frequencies with a range from 0 to 68 million. TH1 cells with anti-leukemic specificity were not detectable. We conclude that there are great inter-individual differences in the GVL potential of fully allogeneic peripheral T lymphocytes. It is possible to identify T cell lines with reactivity against leukemia blasts and non-reactivity against normal hematological cells from the same individual. These cell lines are potential effector cells for immunotherapy of human leukemia.

Blood Donors↗
PubMed1994

Failure of in vitro T-cell assays to predict clinical outcome after human kidney transplantation.

Allotransplant rejection is a T-cell-dependent reaction. Functional in vitro T-cell assays are being used widely for donor-recipient matching in bone marrow transplantation and have recently been used in some centres for transplant monitoring. In order to assess tolerance induction after clinical transplantation, we measured the T-cell response of the host against donor spleen cells of 33 kidney transplant patients before and every 3 months after transplantation over a period of 18 months. The T-cell reactivity before transplantation was not significantly different in any of the assays in rejecting and non-rejecting patients. In the classical mixed lymphocyte culture (MLC), a donor-specific loss of reactivity was seen only in a patient with a CMV-associated irreversible transplant rejection. One patient with chronic rejection acquired a very high MLC response against donor spleen cells and a high response against third-party cells. Little or nonspecific changes were seen in the MLCs of all other patients. Using the method of limiting dilution analysis (LDA), we found a significant reduction of donor-specific cytotoxic T-cell precursors (CTL-p) within the first 3 months after transplantation in most patients with high antidonor CTL-p frequencies before transplantation. The reduction of donor-specific CTL-p was seen in patients with rejection episodes as well as in patients without. Thus we conclude, in contrast to others, that MLC and CTL-p LDA have no predictive value on the outcome of clinical transplantation.

Clonal Deletion↗
PubMed1993

Interleukin-4 bypass of the immunosuppressive effect mediated by interleukin-2 receptor antibodies.

Numerous studies have demonstrated that the generation of alloreactive effector cells depends on cytokines. Conversely, there is evidence that cytokine metabolism is altered at the clonal level in tolerant chimaeras. This has led to preclinical and clinical studies using antibodies that antagonize interleukin-2 (IL-2), with the hope of achieving immunosuppression and inducing tolerance. Monoclonal antibodies against the alpha-chain (p55) of the human IL-2 receptor are being applied to prevent transplant rejection and graft-versus-host disease in several clinical trials. The antibodies that have been applied clinically so far antagonize the binding of IL-2 to the IL-2 receptor alpha-chain which is part of the high affinity IL-2 receptor, but they do not deplete the receptor-bearing cells. Our study investigates the immunosuppressive effect of monoclonal antibodies against the alpha-chain (p55) and beta-chain (p75). In mixed lymphocyte cultures the p55 antibody causes a reduction in T-cell proliferation to about 50%. The generation of cytotoxic T cells is reduced more effectively (up to 80%). By additional blocking of the IL-2 receptor beta-chain we achieved an additional but still incomplete immunosuppressive effect. Moreover we show that IL-2 receptor-blocked alloreactive T cells escape suppression by using IL-4 as an alternative stimulating signal. To prevent T lymphocytes benefiting from this alternative and thwarting the immunosuppressive effect, cytotoxic IL-2 receptor antibodies that deplete the high affinity receptor-bearing cells are needed.

Antibodies↗
PubMed1992

Rejection prophylaxis with interleukin-2 receptor antibody BT 563: mechanisms of action on human cells.

We investigated the in vitro immunosuppressive effect of BT 563, a monoclonal antibody, against the alpha-chain of the human interleukin-2 (IL-2) receptor (p 55), which has been used to prevent transplant rejection in several clinical trials. We also measured the proliferative T cell alloresponse and pCTL frequencies of BT563-treated kidney transplant patients. In mixed lymphocyte cultures BT 563 caused a reduction of T cell proliferation to about 50%. This could not be reversed by the addition of exogenous IL-2. A more effective reduction (80%) was seen in the generation of cytotoxic T cells from CML cultures and at the clonal level. The specific T cell response after preincubation with antigen and BT 563 was not reduced so that BT 563 did not induce tolerance. The in vitro findings indicated that BT 563 had a significant but incomplete immunosuppressive effect. This correlated with the clinical course and ex vivo analysis of PBL from BT 563-treated patients after kidney transplantation.

Antibodies, Monoclonal↗