TY  - JOUR
AB  - BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) is the therapy of choice for selected patients with complicated type 1 diabetes mellitus and end-stage renal disease. Pancreas rescue allocation was implemented in Eurotransplant allocation algorithms to increase organ utilization, concurrently facilitating transplantation of supposedly inferior quality organs. The aim of this study was to examine whether outcomes of SPKT after rescue allocation, which can either be recipient-oriented extended allocation or competitive rescue allocation, were as good as after standard allocation. METHODS: This retrospective multicenter analysis of 1504 SPKT performed from 2013 to 2021 evaluated outcomes by allocation type considering survival of patients, pancreas grafts, and kidney grafts. Multivariable analyses further explored the influence of specific donor-, recipient-, and transplant-related variables on outcomes. RESULTS: Multivariable analyses showed no significant differences in SPKT outcome for standard allocation versus either rescue allocation type regarding patient, pancreas graft, and kidney graft survival. Rescue allocation organ donors were older, had higher body mass index, and were more likely to smoke. Rescue allocation had fewer HLA matches. Cold ischemic times of both pancreas and kidneys were longer in competitive rescue allocation but not in recipient-oriented extended allocation. Rescue allocation pancreas recipients had shorter waiting times. Multivariable analyses showed inferior pancreas and kidney graft survival for higher donor age. Higher recipient age correlated with higher mortality despite better pancreas graft survival. CONCLUSIONS: SPKT outcome after rescue allocation is comparable with standard allocation in both patient and graft survival. Age of both donors and recipients essentially influences the success of SPKT.
AU  - Assfalg, V.*
AU  - Stocker, F.*
AU  - Hüser, N.*
AU  - Hartmann, D.*
AU  - Matevossian, E.*
AU  - van Bruchem, M.*
AU  - Vogelaar, S.*
AU  - Renders, L.*
AU  - Schmaderer, C.*
AU  - Margreiter, C.*
AU  - Deák, A.*
AU  - Messner, F.*
AU  - Kammer, M.*
AU  - Ysebaert, D.*
AU  - Jacobs-Tulleneers-Thevissen, D.*
AU  - Michalski, D.*
AU  - van Laecke, S.*
AU  - Gillard, P.*
AU  - Kahl, A.*
AU  - Viebahn, R.*
AU  - Riediger, C.*
AU  - Jänigen, B.*
AU  - Schmelzle, M.*
AU  - von Samson-Himmelstjerna, F.A.*
AU  - Stippel, D.*
AU  - Harth, A.*
AU  - Nitschké, M.J.E.*
AU  - Koliogiannis, D.*
AU  - Pascher, A.*
AU  - Hoyer, J.*
AU  - Weinmann-Menke, J.*
AU  - Schiffer, M.*
AU  - Hinz, S.*
AU  - Nadalin, S.*
AU  - Lopau, K.*
AU  - Huurman, V.*
AU  - Arnol, M.*
AU  - Miller, G.
C1  - 73640
C2  - 57152
SP  - 1437-1448
TI  - Combined pancreas-kidney transplantation after rescue allocation: The eurotransplant experience: A retrospective multicenter outcome analysis.
JO  - Transplantation
VL  - 109
IS  - 8
PY  - 2025
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - The outcome after liver transplantation has improved in recent years, which can be attributed to superior storage and transportation conditions of the organs, as well as better peri- and postoperative management and advancements in surgical techniques. Nevertheless, there is an increasing discrepancy between the need for organs and their availability. Consequently, the mortality rate on the waiting list is high and continues to rise. One way of counteracting this trend is to increase the use of "expanded criteria donors." This means that more and more donors will be included, especially those who are older and having additional comorbidities (eg, steatosis). A major complication of any transplantation is the occurrence of ischemia/reperfusion injury (IRI), which often leads to liver dysfunction and failure. However, there have been various promising approaches to minimize IRI in recent years, but an effective and clinically applicable method to achieve a better outcome for patients after liver transplantation is still missing. Thereby, the so-called marginal organs are predominantly affected by IRI; thus, it is crucial to develop suitable and effective treatment options for patients. Recently, regulated cell death mechanisms, particularly ferroptosis, have been implicated to play a major role in IRI, including the liver. Therefore, inhibiting this kind of cell death modality presents a promising therapeutic approach for the management of this yet untreatable condition. Thus, this review provides an overview of the role of ferroptosis in liver IRI and transplantation and discusses possible therapeutic solutions based on ferroptosis inhibition to restrain IRI in marginal organs (especially steatosis and donation after circulatory death organs).
AU  - Eggenhofer, E.*
AU  - Proneth, B.
C1  - 71749
C2  - 56425
CY  - Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
SP  - E228-E236
TI  - Ferroptosis inhibition: A key opportunity for the treatment of Ischemia/reperfusioninjury in liver transplantation.
JO  - Transplantation
VL  - 109
IS  - 5
PB  - Lippincott Williams & Wilkins
PY  - 2024
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - BACKGROUND: Baseline lung allograft dysfunction (BLAD) is characterized by the failure to achieve normal baseline lung function after double lung transplantation (DLTX) and is associated with a high risk of mortality. In single lung transplant (SLTX) recipients, however, cutoff values and associated factors have not been explored. Here, we aimed to define BLAD in SLTX recipients, investigate its impact on allograft survival, and identify potential risk factors for BLAD in SLTX recipients. METHODS: We performed a retrospective, single-center analysis of the LTX cohort of LMU Munich between 2010 and 2018. In accordance with DLTX cutoffs, BLAD in SLTX recipients was defined as failure to achieve percentage of forced expiratory volume in 1 s and percentage of forced vital capacity of >60% on 2 consecutive tests >3 wk apart. Survival analysis and regression analysis for potential predictors of BLAD were performed. RESULTS: In a cohort of 141 SLTX recipients, 43% of patients met BLAD criteria. SLTX recipients with BLAD demonstrated impaired survival. Native lung hyperinflation was associated with BLAD in obstructive disease, whereas donor/recipient lung size mismatch was associated with BLAD in both obstructive and restrictive underlying diseases. Pulmonary function testing at 3 mo after lung transplantation predicted normal baseline lung function in SLTX recipients with obstructive lung disease. CONCLUSIONS: BLAD in SLTX recipients is as relevant as in DLTX recipients and should generally be considered in the follow-up of LTX recipients. Risk factors for BLAD differed between underlying obstructive and restrictive lung disease. A better understanding of associated factors may help in the development of preventive strategies.
AU  - Gerckens, M.
AU  - Mümmler, C.
AU  - Richard, A.*
AU  - Strodel, J.*
AU  - Mertsch, P.*
AU  - Milger, K.*
AU  - Veit, T.*
AU  - Gade, N.*
AU  - Yildirim, A.Ö.
AU  - Schneider, C.*
AU  - Kauke, T.*
AU  - Michel, S.
AU  - Irlbeck, M.*
AU  - Behr, J.*
AU  - Kneidinger, N.*
C1  - 71646
C2  - 56330
TI  - Characterization of baseline lung allograft dysfunction in single lung transplant recipients.
JO  - Transplantation
PY  - 2024
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Eggenhofer, E.*
AU  - Proneth, B.
AU  - Doll, S.
AU  - Seebauer, L.*
AU  - Conrad, M.
AU  - Schlitt, H.*
AU  - Geissler, E.*
C1  - 54497
C2  - 45577
CY  - Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
SP  - S713-S713
TI  - Targeting innate immune cells and regulated cell death in early hepatic ischemia reperfusion injury.
JO  - Transplantation
VL  - 102
PB  - Lippincott Williams & Wilkins
PY  - 2018
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - Recent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus infection. Because patients with different liver disease stages have been treated with great success including those awaiting liver transplantation, therapy has been extended to patients with hepatocellular carcinoma as well. From observational studies among compensated cirrhotic hepatitis C patients treated with interferon-containing regimens, it would have been expected that the rate of hepatocellular carcinoma occurrence is markedly decreased after a sustained virological response. However, recently 2 studies have been published reporting markedly increased rates of tumor recurrence and occurrence after viral clearance with DAA agents. Over the last decades, it has been established that chronic antigen stimulation during persistent infection with hepatitis C virus is associated with continuous activation and impaired function of several immune cell populations, such as natural killer cells and virus-specific T cells. This review therefore focuses on recent studies evaluating the restoration of adaptive and innate immune cell populations after DAA therapy in patients with chronic hepatitis C virus infection in the context of the immune responses in hepatocarcinogenesis.
AU  - Werner, J.M.*
AU  - Adenugba, A.*
AU  - Protzer, U.
C1  - 52829
C2  - 44192
SP  - 904-909
TI  - Immune reconstitution after HCV clearance with direct antiviral agents: Potential consequences for patients with HCC?
JO  - Transplantation
VL  - 101
IS  - 5
PY  - 2017
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Bartlett, S.T.*
AU  - Markmann, J.F.*
AU  - Johnson, P.*
AU  - Korsgren, O.*
AU  - Hering, B.J.*
AU  - Scharp, D.*
AU  - Kay, T.W.*
AU  - Bromberg, J.*
AU  - Odorico, J.S.*
AU  - Weir, G.C.*
AU  - Bridges, N.D.*
AU  - Kandaswamy, R.*
AU  - Stock, P.*
AU  - Friend, P.*
AU  - Gotoh, M.*
AU  - Cooper, D.K.*
AU  - Park, C.G.*
AU  - OʼConnell, P.*
AU  - Stäbler, C.*
AU  - Matsumoto, S.*
AU  - Ludwig, B.
AU  - Choudhary, P.*
AU  - Kovatchev, B.*
AU  - Rickels, M.R.*
AU  - Sykes, M.*
AU  - Wood, K.*
AU  - Kraemer, K.*
AU  - Hwa, A.*
AU  - Stanley, E.*
AU  - Ricordi, C.*
AU  - Zimmerman, M.*
AU  - Greenstein, J.*
AU  - Montanya, E.*
AU  - Otonkoski, T.*
C1  - 47822
C2  - 39520
SP  - S1-S44
TI  - Report from IPITA-TTS opinion leaders meeting on the future of β-cell replacement.
JO  - Transplantation
VL  - 100
PY  - 2016
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.
AU  - Markmann, J.F.*
AU  - Bartlett, S.T.*
AU  - Johnson, P.*
AU  - Korsgren, O.*
AU  - Hering, B.J.*
AU  - Scharp, D.*
AU  - Kay, T.W.*
AU  - Bromberg, J.*
AU  - Odorico, J.S.*
AU  - Weir, G.C.*
AU  - Bridges, N.D.*
AU  - Kandaswamy, R.*
AU  - Stock, P.*
AU  - Friend, P.*
AU  - Gotoh, M.*
AU  - Cooper, D.K.*
AU  - Park, C.G.*
AU  - OʼConnell, P.J.*
AU  - Stäbler, C.*
AU  - Matsumoto, S.*
AU  - Ludwig, B.
AU  - Choudhary, P.*
AU  - Khovatchev, B.*
AU  - Rickels, M.R.*
AU  - Sykes, M.*
AU  - Wood, K.*
AU  - Kraemer, K.*
AU  - Hwa, A.*
AU  - Stanley, E.*
AU  - Ricordi, C.*
AU  - Zimmerman, M.*
AU  - Greenstein, J.*
AU  - Montanya, E.*
AU  - Otonkoski, T.*
C1  - 48408
C2  - 41043
CY  - Philadelphia
SP  - E25-E31
TI  - Executive summary of IPITA-TTS opinion leaders report on the future of β-cell replacement.
JO  - Transplantation
VL  - 100
IS  - 7
PB  - Lippincott Williams & Wilkins
PY  - 2016
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Kemter, E.*
AU  - Cohrs, C.M.*
AU  - Wolf, A.*
AU  - Wuensch, A.*
AU  - Kurome, M.*
AU  - Kessler, B.*
AU  - Zakhartchenko, V.*
AU  - Loehn, M.*
AU  - Ivashchenko, Y.*
AU  - Speier, S.
AU  - Schulte, A.*
AU  - Wolf, E.*
C1  - 47874
C2  - 39707
SP  - S99
TI  - INS-EGFP transgenic piglets provide a novel tool for studying maturation and vascularization of Neonatal Islet Cell Clusters (NICCs) in vivo.
JO  - Transplantation
VL  - 99
PY  - 2015
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Ludwig, B.
AU  - Ludwig, S.*
AU  - Steffen, A.
AU  - Zimerman, B.*
AU  - Schmid, J.*
AU  - Schubert, U.*
AU  - Heinke, S.*
AU  - Knauf, Y.*
AU  - Kaup, F.*
AU  - Goldman, T.*
AU  - Barkai, U.*
AU  - Rotem, A.*
AU  - Bornstein, S.R.
C1  - 47869
C2  - 39712
SP  - S31
TI  - Preclinical studies on porcine islet macroencapsulation in non-human primates.
JO  - Transplantation
VL  - 99
PY  - 2015
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Ludwig, B.
AU  - Lehmann, S.*
AU  - Schmid, J.*
AU  - Schubert, U.*
AU  - Steffen, A.
AU  - Bornstein, S.R.
C1  - 47873
C2  - 39708
SP  - S123
TI  - Attenuation of immunosuppression related negative effects on islet grafts by Growth Hormone Releasing Hormone (GHRH) agonist.
JO  - Transplantation
VL  - 99
PY  - 2015
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Steffen, A.
AU  - Müller, A.
AU  - Bornstein, S.R.
AU  - Ludwig, B.
C1  - 47870
C2  - 39711
SP  - S294
TI  - The influence of previous pregnancy on the functionality of smaller and larger rat islets.
JO  - Transplantation
VL  - 99
PY  - 2015
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Steffen, A.
AU  - Ludwig, S.*
AU  - Schmid, J.
AU  - Schubert, U.
AU  - Weitz, J.*
AU  - Bornstein, S.R.
AU  - Ludwig, B.
C1  - 47871
C2  - 39710
SP  - S197
TI  - Pig pancreas preservation and the influence on islet isolation outcome.
JO  - Transplantation
VL  - 99
PY  - 2015
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Steffen, A.
AU  - Lehmann, S.
AU  - Balyura, M.
AU  - Bornstein, S.R.
AU  - Ludwig, B.
C1  - 47872
C2  - 39709
SP  - S184
TI  - The influence of age on islet size distribution in male and female rats.
JO  - Transplantation
VL  - 99
PY  - 2015
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - BACKGROUND: After allogeneic hematopoietic stem-cell transplantation (HSCT), donor-derived T cells may elicit graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) responses. The main targets of GVHD and GVT responses after human leukocyte antigen (HLA)-identical HSCT are minor histocompatibility antigens (mHAgs), that is, polymorphic gene products in which recipient and donor differ. Thus, for increasing beneficial GVT and decreasing life-threatening GVHD responses, knowledge of the relevant mHags is required. Here, we sought to identify mHags recognized by CD4 T cells using a novel serologic approach. METHODS: To identify candidate mHAgs recognized by CD4 T cells, a cDNA expression library from peripheral blood mononuclear cells of a patient with β-thalassemia major was screened with serum taken at different time points after HLA-identical HSCT.. RESULTS: Immune responses against 18 antigens were identified with serum taken 100 days posttransplantation, when the patients had recovered from acute GVHD II. Except for one, no humoral responses against these antigens were detected 25 days or 1 year after transplantation. Sequence comparison of these antigens between recipient and donor revealed three polymorphisms of which two were contained within epitopes predicted to bind to HLA-DR molecules of the patient. Using cytokine secretion and capture assays, T cells specific for the polymorphic antigens of the recipient, but not the donor, were isolated from peripheral blood monocyte cells after HSCT. CONCLUSIONS: The serologic approach described here facilitates the rapid identification of mHAgs recognized by CD4 T cells. Furthermore, the correlation of humoral and cellular immune responses with acute GVHD implies a role of these antigens in GVHD pathology.
AU  - Milosevic, S.
AU  - Bachnick, B.*
AU  - Karim, K.
AU  - Bornkamm, G.W.
AU  - Witter, K.*
AU  - Gerbitz, A.*
AU  - Mautner, J.
AU  - Behrends, U.
C1  - 4836
C2  - 27962
SP  - 1030-1035
TI  - Identification of MHC II-restricted minor histocompatibility antigens after HLA-identical stem-cell transplantation.
JO  - Transplantation
VL  - 90
IS  - 9
PB  - Lippincott Williams & Wilkins
PY  - 2010
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Pihusch, R.*
AU  - Salat, C.*
AU  - Schmidt, E.*
AU  - Göhring, P.*
AU  - Pihusch, M.*
AU  - Hiller, E.*
AU  - Holler, E.*
AU  - Kolb, H.-J.
C1  - 9839
C2  - 21132
SP  - 1303-1309
TI  - Hemostatic complications in bone marrow transplantation : a retrospective analysis of 447 patients. 
JO  - Transplantation
VL  - 74
PY  - 2002
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - Antibodies against T cells are widely used as immunosuppressive agents in clinical therapy. As effector functions of chimeric or humanized anti-T cell antibodies cannot be predicted in vitro, we compared T cell-depleting effects of human isotypes in vivo with their immunosuppressive consequences in a mouse BMT model. This system is based on chimeric antibodies with a mouse pan T cell specificity and human constant regions. To secure optimal immunosuppression, the specificity for Thy-1.2--one of the best-characterized T cell antigens--was selected, as Thy-1.2-specific antibodies prevent graft-versus-host disease in fully mismatched mice. Chimeric mouse anti-Thy-1.2 antibody with the human IgG1 Fc part was found to be equally effective in preventing graft-versus-host disease mortality as the highly protective anti-Thy-1.2 mouse IgG2a isotype, while human IgG3 was far less effective. This was not predictable by measuring the degree of T cell depletion in peripheral blood. T cell depletion in lymph nodes, however, exactly reflected the results obtained in the BMT system. In addition, this system offers the advantage of assessing the influence of reduced antigen density by using heterozygous Thy-1.2 mice.
AU  - Mocikat, R.
AU  - Kütemeier, G.
AU  - Hoffmann-Fezer, G.
AU  - Thierfelder, S.
C1  - 58136
C2  - 0
SP  - 405-11
TI  - A mouse model for the preclinical evaluation of immunosuppressive effector functions of human isotypes. The human IgG1 isotype is superior to IgG3.
JO  - Transplantation
VL  - 57
IS  - 3
PY  - 1994
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Reinecke, K.
AU  - Mysliwietz, J.
AU  - Thierfelder, S.
C1  - 49533
C2  - 31287
SP  - 458-461
TI  - Single as well as pairs of synergistic anti-CD4+CD8 antibodies prevent graft-versus-host disease in fully mismatched mice.
JO  - Transplantation
VL  - 57
IS  - 3
PY  - 1994
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Marz, W.
AU  - Peschke, B.
AU  - Ruzicka, V.
AU  - Siekmeier, R.
AU  - Gross, W.
AU  - Schoeppe, W.
AU  - Scheuermann, E.
C1  - 20649
C2  - 13863
SP  - 284-288
TI  - Type III Hyperlipoproteinemia Acquired by Liver Transplantation.
JO  - Transplantation
VL  - 55
PY  - 1993
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Mysliwietz, J.
AU  - Thierfelder, S.S.
C1  - 40262
C2  - 0
SP  - 1266-1269
TI  - Coinjection of anti-interleukin-2 receptor antibody diminishes antiantibody formation during prolonged treatment with anti-CD3 antibody.
JO  - Transplantation
VL  - 56
IS  - 5
PY  - 1993
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Mysliwietz, J.
AU  - Thierfelder, S.
AU  - Hoffmann-Fezer, G.
AU  - Kummer, U.
C1  - 18301
C2  - 11053
SP  - 749-755
TI  - Antilymphocytic Antibodies and Bone Marrow Transplantation. XI. Evidence that Reduce Thy-1  Expression in Thy-1.1 Mice Prevents Suppression of Graft-Versus-Host Disease with Anti-Thy-1 Monoclonal Antibodies.
JO  - Transplantation
VL  - 49
PY  - 1990
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - Considerable variations in the suppression of graft-versus-host disease with monoclonal anti-Thy-1 antibodies were found to relate to substantial differences noted in the expression of mouse Thy-1 marker on lymph node and spleen cells of Thy-1.1 (AKR/J, C57BL/6.Thy-1.1) and Thy 1.2 (AKR/Cu, C57BL/6) mice. Thy-1.1 mice showed a population of 22% (AKR/J) or 13% (C57BL/6-Thy-1.1) of Thy-1 negative cells among peripheral T cells carrying Ly-1 marker. This was in sharp contrast with Thy-1.2 mice, where as expected practically all peripheral T cells expressed both Thy-1 and Ly-1. Double-marker analysis on FACScan revealed that the Thy-1-/Ly-1+ cell population identified in Thy-1.1 but not in Thy-1.2 mice doubtless represents T cells because they express CD3 and either the L3T4 (CD4) or Lyt2 (CD8) phenotype. Using quantitative fluorescence-measurement techniques, it was found in addition that the Thy-1 antigen-binding sites on Thy-1+ cells from Thy-1.1 mice are considerably fewer than those present in Thy-1.2 mice. In fact, Thy-1 antigen-binding sites approximate the level of Ly-1 density. Consequences of the reduced expression of Thy-1 became apparent in vivo: (1) lymphnode and splenic T cell areas in Thy-1.1 mice were clearly less depleted when Thy-1.1 and Thy-1.2 mice had been injected with rat IgG2b anti-Thy-1 mAb; and (2) GvHD was prevented completely in fully mismatched mice by anti-Thy-1 mAb if the donor mice expressed Thy-1.2 but was barely delayed if the donors expressed Thy-1.1. Thus the present study provides a transplantation model for comparing differences in T antigen density and their consequences for antibody-induced immunosuppression.
AU  - Mysliwietz, J.
AU  - Thierfelder, S.S.
AU  - Hoffmann-Fezer, G.
AU  - Kummer, U.
C1  - 41799
C2  - 36470
SP  - 749-755
TI  - Antilymphocytic antibodies and bone marrow transplantation: XI. Evidence that reduced Thy-1 expression in Thy-1.1 mice prevents suppression of graft-versus-host disease with anti-Thy-1 monoclonal antibodies.
JO  - Transplantation
VL  - 49
IS  - 4
PY  - 1990
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - Timing, magnitude, and effect of the murine antibody response to rat pan-T-cell antibodies were studied in a bone marrow (C57BL/6-to-CBA mice) transplantation model. Prospective C57BL/6 marrow donor mice were sensitized against pan-T-cell (Thy-1, Thy-1.2, Lyt-1) monoclonal antibodies of various rat isotypes or against polyclonal rat antimouse-thymocytes (rat ATG) antibodies. Three days prior to transfer of spleen and bone marrow cells, the sensitized C57BL/6 donors received a dose of anti-Thy-1 mAb (RmT1) known to abolish graft-versus-host reactivity of unsensitized donors. The injected mAb provoked anti-antibodies reacting with RmT1. The anti-antibodies inhibited immunosuppression of the rat mAb RmT1 even if they bound only to nonidiotypic epitopes on RmT1. Avoiding cell-binding of the sensitizing rat anti-Thy-1.2 mAb by its injection into Thy-1.1 mice induced only low-titer and delayed anti-antibodies. This indicated the enhanced immunization potential of anti-Thy-1 when bound to cells. Finally, sensitization leading to the mouse antirat anti-antibodies and reversion of immunosuppression was prevented or reduced considerably by T cell depletion with a mouse IgG2a anti-Thy-1.2 mAb or high-dose cyclophosphamide or by rabbit ATG, provided it was initiated before starting the sensitizing injections of the rat antimouse T cell antibodies.
AU  - Kremmer, E.
AU  - Thierfelder, S.S.
AU  - Kummer, U.
AU  - Lederer, R.
AU  - Mysliwietz, J.
C1  - 41920
C2  - 10494
SP  - 641-646
TI  - Neutralization of immunosuppression by antibodies against variable as well as constant regions of monoclonal anti-Thy-1 xenoantibodies and their ability to be suppressed by initial T cell depletion.
JO  - Transplantation
VL  - 47
IS  - 4
PY  - 1989
SN  - 0041-1337
ER  - 

TY  - JOUR
AU  - Thierfelder, S.
AU  - Hoffmann-Fezer, G.
AU  - Kremmer, E.
C1  - 17890
C2  - 10908
SP  - 511-514
TI  - Evidence that initial T cell depletion suppresses antiantibody formation and preserves immunosuppression after polyclonal ATG.
JO  - Transplantation
VL  - 48
IS  - 3
PY  - 1989
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - Pairs of murine monoclonal antibodies, which recognize 2 different epitopes on a single antigen are described. These antibodies (MdT-P1, -P2, -Q1, -Q2) defining a canine pan-T cell antigen, were raised against dog thymocytes. In immunoblotting of solubilized and polyacrylamide gradient gel electrophoresis in sodium dodecyl sulphate (SDS-PAGE) fractionated dog thymocytes, they revealed a strong heterogeneous antigen. Competitive inhibition of binding of directly labeled mouse-antidog T lymphocytes monoclonal antibodies (MdT-mAbs) to solubilized dog thymocytes indicates that 2 different antigenic epitopes (P, Q) are recognized. In direct peroxidase immunocytochemistry, MdT monoclonal antibodies recognized up to 95% thymocytes, 69% blood lymphocytes, 76% lymph node lymphocytes, and approximately 2% bone marrow lymphocytes; they were nonreactive with surface immunoglobulin positive blood cells, monocytes, platelets, cells of myelo- and erythropoietic lineage in the bone marrow. Immunohistochemistry on thymus, lymph nodes, and spleen sections revealed that MdT-mAbs had labeled cortical and medullary thymocytes, paracortical T cell areas in pulp, whereas B cell areas remained unstained. The antibodies lysed dog thymocytes in the presence of complement. Lethally irradiated dog receiving bone marrow autograft depleted of MdT-P1 positive cells ex vivo showed engraftment and complete recovery of marrow function. Studies of antibody activity on canine hemopoietic progenitor cells in granulocyte-macrophage progenitors (CFU(GM)) also showed no reduction of CFU(GM) in MdT-P1-depleted bone marrow.
AU  - Mysliwietz, J.
AU  - Hoffmann-Fezer, G.
AU  - Thierfelder, S.S.
AU  - Kolb, H.J.
AU  - Maldacker, J.
C1  - 41629
C2  - 40534
SP  - 443-448
TI  - Recognition of two epitopes of an antigen present on canine T cells but not on hemopoietic progenitors by four monoclonal antibodies.
JO  - Transplantation
VL  - 45
IS  - 2
PY  - 1988
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - The in vivo and in vitro effectiveness of several monoclonal antimouse T and B cell antibodies, of anti-Th-1 and of Ia(k) serum, as well as of ATG were compared. The parameters were prolongation of skin graft survival, prevention of graft-versus-host disease (GVHD), antibody and primary and secondary plaque formation against sheep red blood cells (RBCs), and T cell depletion of lymphoid tissues. In general, in vitro effectiveness of the monoclonal antibodies exceeded their in vivo effectiveness. Skin graft survival was prolonged by ATG, but not by monoclonal anti-T, or anti-T plus anti-B antibody. GVHD was prevented by in vitro incubation of donor bone marrow with monoclonal anti-Th-1, but in vivo treatment of marrow donors was ineffective. Treatment with ATG was successful. Anti Ia(k) antibody blocked plaque formation by spleen cells incubated with sheep RBCs, but had no effect on secondary plaque formation when given in vivo. Neither was there any in vivo effect of anti-Ia(k) or anti-Th-1 on antisheep RBC agglutinin formation. ATG was effective in both of these assays, although its cytotoxic and complement-fixing titer did not exceed that of anti-Th-1 or anti-Ia(k). Although anti-Th-1 was cleared more rapidly from the serum of mice expressing the corresponding Th-1 alloantigen, than from mice with the noncorresponding alloantigen and although anti-Th-1 was shown to bind to the T cell areas of the lymphoid tissue, it did not - unlike ATG - deplete these areas of T cells. Possible reasons for the difference in effectiveness of in vitro and in vivo application of these monoclonal antibodies are discussed.
AU  - Thierfelder, S.S.
AU  - Hoffmann-Fezer, G.
AU  - Rodt, H.V.
AU  - Doxiadis, I.I.N.*
AU  - Eulitz, M.*
AU  - Kummer, U.*
C1  - 41616
C2  - 38490
SP  - 249-254
TI  - Antilymphocytic antibodies and marrow transplantation. VI. Absence of immunosuppression in vivo after injection of monoclonal antibodies blocking graft-versus-host reactions and humoral antibody formation in vitro.
JO  - Transplantation
VL  - 35
IS  - 3
PY  - 1983
SN  - 0041-1337
ER  - 

TY  - JOUR
AB  - Bone marrow removed from leukemic patients during remission, for retransplantation during relapse, may contain residual leukemic cells. Antisera against surface antigens of these cells should not react with hemopoietic stem cells. In order to produce an appropriate antiserum, rabbits were given injections of cells from the common form of acute lymphoblastic leukemia (cALL) of childhood. The resultant antiserum was absorbed with liver-kidney homogenate, chronic lymphoid leukemia cells (CLL), normal peripheral lymphocytes, and lymphoblastoid cells from B cell lines. The purified globulin fraction showed high complement-dependent cytotoxicity against the cells of 39 of 56 patients with ALL. It did not react with the cells of 11 T-ALL, 1 B-ALL, and 5 undifferentiated (without known markers) ALL. Furthermore, the antiserum did not react with the cells from acyte myeloid leukemias, chronic lymphoid leukemias, B-type lymphoblastoid cell lines, normal bone marrow cells, and peripheral blood lymphocytes. Unabsorbed anti-cALL globulin was found to be highly cytotoxic against hemopoietic colony-forming cells (CFU-c) and completely inhibited the growth of marrow cells and CFU-c in diffusion chambers. Absorption of anti-cALL with liver-kidney homogenate, CLL, and peripheral blood lymphocytes removed only part of the cytotoxic antibodies cross-reacting with antigens present on CFU-c. An additional absorption with lymphoblastoid cell lines removed the cytotoxic effect of anti-cALL against CFU-c completely and did not inhibit proliferation of marrow cells and CFU-c in diffusion chambers, while high cytotoxicity against cALL blasts was preserved. It follows that cALL antiserum lacks an inhibitory effect on normal hemopoietic stem cells when measured in CFU-c and diffusion chamber assays.
AU  - Netzel, B.
AU  - Rodt, H.V.
AU  - Lau, B.
AU  - Thiel, E.V.*
AU  - Haas, R.J.*
AU  - Dörmér, P.G.*
AU  - Thierfelder, S.S.*
C1  - 41329
C2  - 35701
SP  - 157-161
TI  - Transplantation of syngeneic bone marrow incubated with leukocyte antibodies : II. Cytotoxic activity of anti-cALL globulin on leukemic cells and normal hemopoietic precursor cells in man.
JO  - Transplantation
VL  - 26
IS  - 3
PY  - 1978
SN  - 0041-1337
ER  -