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Biomedical subjects

O Witzke

Publications and source records attributed to O Witzke.

At least 19 recordsLinked to original sources
PubMed2007

[Wegener's granulomatosis and orbital complications of sino-nasal origin].

Wegener's granulomatosis is an idiopathic, granulomatous disease with the potential for multiple head and neck manifestations (80 % of the patients). Sinonasal symptoms are observed in more than 60 % of the patients. Due to these facts the otorhinolaryngologist plays an essential role in the multidisciplinary team involved in establishing the diagnosis early, initiating immunosuppressive therapy and providing ongoing care. The treatment is based on medical therapy consisting of corticosteroids and immunosuppressive agents, whereas surgery is reserved for selected head and neck manifestations. By means of 3 patients presenting with distinct visual loss in consequence of orbital complications with sinonasal origin the course of disease and theoretical background are reviewed. In our patients Wegener's granulomatosis was diagnosed by histopathological examination and serological detection of ANCA, cANCA. The progression of the granulomatous process and an additional purulent inflammation in 2 cases led to a temporary amaurosis and in another case to a visual loss of 50 %. Immediate orbital decompression in combination with sufficient systemic immunosuppressive treatment relieved the compression of the optical nerve and preserved vision. We conclude that early orbital decompression either by external or endonasal approach and concomitant immunosuppression is necessary to determine or improve rapidly decreasing vision subsequent to high intraorbital pressure produced by a granulomatous process and inflammation.

Anti-Bacterial Agents↗
PubMed2006

CD134 expression on CD4+ T cells is associated with nephritis and disease activity in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by a deviation of the immune system that involves T cell-dependent autoantibody production. The aim of this study was to investigate the role of co-stimulatory markers on T cells in this disease. Twenty-eight patients with SLE as defined by the American College of Rheumatology (ACR) criteria and 11 healthy controls were included into the study. Eleven patients had biopsy-proven lupus nephritis while 17 patients had no clinical evidence of lupus nephritis. Clinical disease activity was assessed according to the systemic lupus erythematosus disease index (SLEDAI). CD4+ T cell populations in the peripheral blood were analysed for the expression of co-stimulatory markers CD45RO, CD70, CD80, CD86, CD137, CD137L, CD134, CD152, CD154 and ICOS. SLE patients showed an increased frequency of peripheral CD4+ T cells expressing high levels of CD80, CD86 and CD134 compared to healthy controls (7.1 +/- 1.5% versus 1.7 +/- 0.9%; P < 0.005; 2.3 +/- 0.4% versus 1.0 +/- 0.2%; P = 0.008, 20.2 +/- 2.0% versus 10.6 +/- 1.9%; P < 0.005, respectively). Significantly higher levels of CD80 on CD4+ T cells were detected in SLE patients with lupus nephritis compared to patients without nephritis (11.9 +/- 3.3% versus 4.0 +/- 0.7%; P < 0.005). There was an increased presence of CD134+ CD4+ cells in SLE patients with lupus nephritis (27.5 +/- 4.0% versus 15.5 +/- 1.3%; P < 0.005). CD80 and CD134 expression was significantly correlated with SLEDAI (r = 0.42, P = 0.03; r = 0.56, P < 0.005). Co-stimulatory molecules on CD4+ T cells are associated with renal disease and disease activity in patients with systemic lupus erythematosus.

Acute Disease↗
PubMed2006

Ezetimibe for the treatment of uncontrolled hypercholesterolemia in patients with high-dose statin therapy after renal transplantation.

We investigated prospectively the efficacy of ezetimibe in addition to statin therapy in stable renal transplant patients in whom hypercholesterolemia was not sufficiently treated. Eighteen renal transplant patients received 10 mg ezetimibe once daily in addition to high-dose statin therapy for uncontrolled hypercholesterolemia. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, Tacrolimus (Tac)- and Cyclosporine A (CsA) blood levels, creatinine, urea, liver enzymes, electrolytes and creatinkinase (CK) were measured before initiation of ezetimibe therapy, after 7 days, 6 weeks and 3 months. Cholesterol concentrations decreased significantly (p < 0.005) from 264 +/- 46 mg/dL at baseline to 205 +/- 48 mg/dL after 1 week to 202 +/- 48 mg/dL after 6 weeks and 212 +/- 40 mg/dL after 3 months (reduction after 3 months 21 +/- 10%). LDL-concentrations decreased significantly (p < 0.005) from 178 +/- 41 mg/dL at baseline to 129 +/- 35 mg/dL after 1 week to 123 +/- 25 after 6 weeks and to 117 +/- 40 mg/dL after 3 months (reduction after 3 months 37 +/- 14%). Two patients stopped ezetimibe therapy due to nausea and muscle pain without CK elevation. Significant changes of CsA and Tac blood levels, liver and muscle enzymes were not observed. Ezetimibe seems to be an effective therapy for uncontrolled hypercholesterolemia in renal transplant patients when combined with high-dose statin therapy.

Adult↗
PubMed2006

Repaglinide in the management of new-onset diabetes mellitus after renal transplantation.

The purpose of this study was to investigate the use of the short-acting insulin secretion drug repaglinide in new-onset diabetes mellitus (NODM) after renal transplantation. Twenty-three Caucasian patients with NODM after renal transplantation were selected to receive repaglinide therapy and were followed for at least 6 months. A control group treated with rosiglitazone was chosen for comparison. Successful repaglinide treatment was defined as a significant improvement of blood glucose concentrations and HbA1c <7% in the absence of glucosuria and without the need for the addition of further anti-diabetic agents. After 6 months of treatment with repaglinide, 14 of the 23 patients were successfully treated. Mean HbA1c decreased from 7.6 +/- 0.6% to 5.8 +/- 0.6% in 14 patients treated successfully. In nine patients, hyperglycemia persisted, and they were switched to insulin treatment (HbA1c 8.5 +/- 2.9% at the beginning to 7.4 +/- 2.2%). Mean serum creatinine levels, cyclosporine A and tacrolimus blood levels did not change significantly following institution of repaglinide therapy. The rate of successful treatment and the degree of HbA1c decrease were similar compared to rosiglitazone-treated control patients. The data from our observational study indicate that repaglinide can be an effective treatment option in Caucasian patients with NODM after renal transplantation.

Carbamates↗
PubMed2005

[Cross-over kidney transplantation in Germany].

A donor kidney exchange or cross-over program with exchange of organs between two donor-recipient pairs offers a possibility to realise living donor renal transplantation in cases of ABO-blood group incompatibility. The German transplantation law demands, in contrast to other countries, a close personal relationship between living donor and recipient. In this paper, we propose a concept based on the generation of a close personal relationship between donor-recipient pairs that allows cross-over renal donor transplantation considering the statement of the responsible medical-ethical institutions and the German transplantation law.

ABO Blood-Group System↗
PubMed2005

Distinct tumour necrosis factor alpha, interferon gamma, interleukin 10, and cytotoxic T cell antigen 4 gene polymorphisms in disease occurrence and end stage renal disease in Wegener's granulomatosis.

BACKGROUND: Cytokines and T cell regulatory proteins play an important role in the pathogenesis of Wegener's granulomatosis (WG). OBJECTIVE: To investigate cytokine and cytotoxic T cell antigen-4 (CTLA4) gene polymorphisms and HLA class II alleles in generalised WG. METHODS: The distribution of cytokine and cytotoxic T cell antigen 4 (CTLA4) gene polymorphisms and HLA class II alleles was analysed in 32 patients with generalised WG and 91 healthy controls. Genotyping was carried out for HLA-DRB1 and HLA-DQB1 and for polymorphism of the genes encoding TNF alpha (-238, -308, -376), TGF beta (codon 10 and 25), IFN gamma (+874), IL6 (-174), IL10 (-592, -819, -1082), CTLA4 (-318, +49), and the (AT)(n) repeats of the CTLA4 gene. In addition, stratification analysis was carried out according to the presence (n = 15) or absence (n = 17) of end stage renal disease. RESULTS: An increase in the IFN gamma +874 T/T (odds ratio (OR) = 3.14) and TNF alpha -238 G/A (OR = 5.01) genotypes was found in WG patients. When ESRD positive and negative patients were compared, the IFN gamma +874 A/A and the CTLA4 -318 C/C genotypes were found more often in the ESRD subgroup (OR = 10.6 and OR = 2.25). WG patients without ESRD had a higher frequency of the IL10 GCC/ACC promotor genotype (OR = 0.13) and long CTLA4 (AT)(n) repeats (OR = 0.4). No effect was seen for HLA-DR and -DQ markers. CONCLUSIONS: Disease susceptibility and clinical course in WG may be associated with distinct polymorphisms of cytokine and CTLA4 genes.

Adult↗
PubMed2001

Suppression mediated by anergic CD4+ T cells requires stimulation by MHC-peptide complexes and can be induced in the presence of costimulation.

BACKGROUND: In this study, we have investigated the mechanisms involved in both the induction of suppressive anergy, the stability of the anergy induced, and the possible mechanisms by which the response of immunocompetent CD4+ T cells are suppressed. METHODS: We used immobilized anti-CD3 monoclonal antibody (mAb) to induce anergy in T helper (Th) 1 and Th0 cells reactive with MHC class II molecule H2 I-Ab. RESULTS: We observed that suppressive anergy was induced independently of costimulation in Th0 but not Th1 cells. Although the anergic and suppressive states of Th0 cells were stable in the presence of exogenous interleukin-2, this was not the case for Th1 cells. No evidence for linked epitope suppression was observed for any of the I-Ab reactive cells investigated. Neither anergy nor suppression was observed in Th0 cells upon restimulation with anti-CD3 in the presence of syngeneic antigen-presenting cells (APCs). However, anergy but not suppression was observed in co-cultures restimulated with anti-T-cell antigen receptor (TCR) mAbs/syngeneic APCs and suppression could be restored by the addition of I-Ab+ APCs. CONCLUSIONS: Overall, these data suggested that the MHC-peptide complex recognized by the Th0 cells was required for suppression of the response of immunocompetent cells. We propose that suppression is mediated either by down-modulation of the MHC-peptide complex recognized by the anergic T cells or that a molecule specific to the MHC-peptide/TCR interaction facilitates negative regulation by APC:T or T:T interactions.

Animals↗
PubMed2001

Critical role for IL-4 in the development of transplant arteriosclerosis in the absence of CD40-CD154 costimulation.

Blockade of the CD40-CD154 pathway can inhibit CD4(+) T cell activation but is unable to prevent immune responses mediated by CD8(+) T cells. However, even in the absence of CD8(+) T cells, inhibition of the CD40-CD154 pathway is insufficient to prevent the development of transplant arteriosclerosis. This study investigated the mechanisms of transplant arteriosclerosis in the absence of the CD40 pathway. C57BL/6 CD40(-/-) (H2(b)) recipients were transplanted with MHC-mismatched BALB/c (H2(d)) aortas. Transplant arteriosclerosis was evident in both CD40(-/-) and CD40(+/-) mice (intimal proliferation was 59 +/- 5% for CD40(-/-) mice vs 58 +/- 4% for CD40(+/-) mice) in the presence or absence of CD8(+) T cells (intimal proliferation was 46 +/- 7% for CD40(-/-) anti-CD8-treated mice vs 50 +/- 10% for CD40(+/-) anti-CD8-treated mice), confirming that CD8(+) T cells are not essential effector cells for the development of this disease. In CD40(-/-) recipients depleted of CD8(+) T cells, the number of eosinophils infiltrating the graft was markedly increased (109 +/- 24 eosinophils/grid for CD40(-/-) anti-CD8-treated mice vs 28 +/- 7 for CD40(+/-) anti-CD8-treated mice). The increased presence of eosinophils correlated with augmented intragraft production of IL-4. To test the hypothesis that IL-4 was responsible for the intimal proliferation, CD8 T cell-depleted CD40(-/-) recipients were treated with anti-IL-4 mAb. This resulted in significantly reduced eosinophil infiltration into the graft (12 +/- 5 eosinophils/grid for CD40(-/-) anti-CD8(+), anti-IL-4-treated mice vs 109 +/- 24 for CD40(-/-) anti-CD8-treated mice), intragraft eotaxin, CCR3 mRNA production, and the level of intimal proliferation (18 +/- 5% for CD40(-/-) anti-CD8(+)-, anti-IL-4-treated mice vs 46 +/- 7% for CD40(-/-) anti-CD8-treated mice). In conclusion, elevated intragraft IL-4 production results in an eosinophil infiltrate and is an important mechanism for CD8(+) T cell-independent transplant arteriosclerosis in the absence of CD40-CD154 costimulation.

Animals↗
PubMed2001

Transient stimulatory effects on pituitary-thyroid axis in patients treated with interleukin-2.

It has been shown that various cytokine therapies may influence thyroid hormone parameters that may lead to serious side effects including nonthyroidal illness. Interleukin-2 is effective in increasing CD4-T cell numbers in human immunodeficiency virus (HIV)-infected patients and it is used in the treatment of various malignant tumours. However, the association of interleukin-2 (IL-2) therapy and thyroid function is not clearly established as serial systematic measurements of thyroid parameters have not been performed with interleukin-2 as the sole therapeutic agent. Therefore, it was the aim of this study to examine prospectively the impact of a 5-day interleukin-2 therapy on thyroid parameters in asymptomatic HIV-infected patients. Twenty male euthyroid patients (mean age, 42.6 +/- 3.2 years; body weight, 73.4 +/- 3.0 kg) received 9,000,000 IU/d interleukin-2. Thyroid function was evaluated by measurements of serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), reverse T3 (rT3), thyroglobulin (Tg), thyroxine-binding globulin (TBG), and anti-thyroid-peroxidase (TPO)-antibodies from day 1-4 and on days 7, 14, 20, 40, 60, 80, and 100. All results are given as mean +/- SD. On day 4, we observed a significant increase that was still within normal range of T4 and T3 (p < 0.05). TSH increased from 1.33 +/- 0.57 to 4.53 +/- 1.39 mU/l (p = 0.0001) and FT4 from 18.1 +/- 4.2 to 48.9 +/- 10.9 pmol/L (p = 0.0001) on day 4 with a gradual decrease thereafter. Normalization to baseline levels for TSH (1.45 +/- 0.75 mU/L) and FT4 (18.1 +/- 3.0 pmol/L) was achieved only on day 14. The increase of FT4 was more pronounced (well in the hyperthyroid range) than the increase in total T4 in the presence of normal TBG and albumin concentrations whereas TBG was not affected. We did not observe changes in anti-TPO-antibody levels up to day 100. Our data clearly demonstrate that the administration of interleukin-2 has a stimulatory effect on the pituitary-thyroid axis. The increase of TSH suggests a central stimulation directed by the action of IL-2 as the major mechanism.

Adult↗
PubMed2001

Impact of febrile infections on the long-term function of kidney allografts.

PURPOSE: We prospectively determined the impact of febrile infectious disease on long-term renal graft function compared with a matched control group. MATERIALS AND METHODS: Included in our study were 39 patients who presented with episodes of febrile infection with body temperature greater than 38C on 2 consecutive occasions, necessitating hospitalization. In addition, 39 controls without febrile infection requiring hospitalization within 2 months were chosen from the complete data pool of all renal transplant recipients followed at our transplant clinic using the matched pair technique. Renal function was estimated by serum creatinine and calculated creatinine clearance. RESULTS: Of the 39 patients with infection 15 had urinary tract infection and 24 had other, mostly bacterial infection, including pneumonia/severe bronchitis in 12, oral/dental infection in 2, gastroenteritis in 2, shunt sepsis in 1, herpes zoster in 1, cytomegalovirus in 1 and other in 5. Mean estimated creatinine clearance plus or minus standard deviation was similar in the infection and control groups at the beginning of the study (51 +/- 22 and 51 +/- 23 ml. per minute, respectively). During the infectious episode mean creatinine clearance significantly decreased to 38 +/- 17 ml. per minute in the infection group. After infection resolved creatinine clearance returned to an almost baseline mean value of 50 +/- 23 ml. per minute. However, after 2 years of followup there was a significant difference in mean creatinine clearance in the infection group versus controls (45 +/- 25 versus 52 +/- 25 ml. per minute, p = 0.022). CONCLUSIONS: To our knowledge we have shown for the first time in a prospective controlled study that febrile infectious episodes correlate with poor long-term renal graft function.

Adult↗
PubMed2000

Islet allograft rejection can be mediated by CD4+, alloantigen experienced, direct pathway T cells of TH1 and TH2 cytokine phenotype.

BACKGROUND: It is widely believed that Thl cells that secrete interferon-gamma are primarily involved in the rejection of allografts whereas Th2 cells [interleukin(IL) 4 and IL-10] are thought to be protective of this process. However, the exact role and specificity of these helper T lymphocytes in mediating allograft damage is presently unknown. METHODS: Th0, Th1, and Th2 cell lines specific for the class II MHC molecule H2IAb were adoptively transferred into T cell deficient, syngeneic, diabetic mice before transplantation of fully allogeneic C57BL/10 (H2b) or (CBKxBALB/c)F1 (H2k/d+Kb) islet grafts. T cells were 5-(and-6-)-carboxyfluorescein diacetate succinimidyl ester- (CFSE) labeled to allow detection, immunohistochemistry was performed, and IL-4 transcripts within the rejected islet grafts were quantified by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Adoptive transfer (IV) of Th0-, Th1-, and Th2 IAb-specific T cells resulted in rejection of H2b islet allografts. CFSE-labeling demonstrated that these T cells were able to home to the graft site. CD4+ T cells and CD11b+ macrophages were present within the graft after adoptive transfer of both Thl and Th2 cells. Interestingly, CD8+ T cells and B cells were absent from these rejecting grafts. Even when Th2 cells were introduced directly at the graft site, prompt rejection was still observed despite the presence of increased IL-4 mRNA expression within the islet allografts. CONCLUSIONS: Th2 and Th0 alloreactive CD4+ T helper cells can reject islet grafts with similar efficiency to Th1 cells. These results suggest that deviation of the immune response from a Th1 to Th2 phenotype will not be sufficient to allow successful engraftment of allogeneic organs or tissues.

Animals↗
PubMed2000

Nondepleting anti-CD4 monoclonal antibody enhances the ability of oral alloantigen delivery to induce indefinite survival of cardiac allografts: oral tolerance to alloantigen.

BACKGROUND: We examined whether oral administration of alloantigen could induce the prolonged survival of cardiac allografts. METHODS: Hearts from CBK (H2k+Kb) transgenic or (C57BL/10xCBA)F1 (H2bxH2k) mice were transplanted into CBA (H2k) recipients pretreated orally with 1 x 10(7) donor splenocytes in the presence or absence of a nondepleting anti-CD4 (YTS 177, 200 microg/dose). RESULTS: Modest prolongation of CBK cardiac grafts was induced in CBA mice fed with multiple doses of CBK splenocytes (MST 42 days compared with controls fed with syngeneic CBA splenocytes, 12 days). When the CD4 monoclonal antibody, YTS177, was administered for 2 days before the first oral delivery of CBK splenocytes, all mice accepted their grafts indefinitely (MST > 100 days versus mice treated with anti-CD4 alone, 11.5 days). To determine if feeding multiple doses of alloantigen was essential, CBA mice were given CBK splenocytes orally on a single occasion in combination with the anti-CD4. The majority of the grafts survived indefinitely (MST >100 days). This oral treatment regimen also induced indefinite prolongation of (C57BL/10xCBA)F1 cardiac grafts. CONCLUSION: The induction of unresponsiveness by oral administration of alloantigen can be augmented by a nondepleting anti-CD4, YTS177, when given before the first oral delivery of allogeneic cells.

Administration, Oral↗
PubMed2000

Intragraft interleukin-4 mRNA expression after short-term CD154 blockade may trigger delayed development of transplant arteriosclerosis in the absence of CD8+ T cells.

BACKGROUND: It has recently been shown that, although anti-CD154 induces CD4+ T-cell tolerance, it is unable to prevent allograft rejection mediated by CD8+ T cells. We have also shown that anti-CD154 monotherapy does not protect the graft from the development of transplant arteriosclerosis even in the absence of CD8+ T cells. This study was designed to investigate and characterize possible mechanisms responsible for the development of transplant arteriosclerosis after CD154 blockade in the absence of CD8+ T cells. METHODS: C57BL/6 (H2b) recipients received a fully MHC-mismatched BALB/c donor aorta (H2d). Animals were either treated with anti-CD154 monoclonal antibody (mAb) in the presence or absence of CD8 T cells. Histology, morphometric measurements, immunohistochemistry, and the production of alloantibodies (IgM, IgG1, IgG2a) were analyzed on days 14, 30, and 50 after transplantation. Cytokine production within the graft was investigated by competitive reverse transcription-polymerase chain reaction on day 14. RESULTS: Combined treatment with anti-CD154 and a depleting CD8 mAb resulted in a delay in the development of transplant arteriosclerosis (intimal proliferation: 33+/-10% vs. 67+/-11% untreated control, day 30) but ultimately did not prevent its progression (intimal proliferation: 55+/-10% vs. 78+/-9% untreated control, day 50). Although there was a significant decrease in the number of CD4+, CD11b+, and CD40+ graft-infiltrating cells and a reduction in the formation of donor-specific IgG1 alloantibodies in recipients treated with anti-CD154 and anti-CD8 mAbs, mRNA for interleukin (IL)-4 was increased, suggesting a shift in the intragraft cytokine profile towards a Th2-like pattern. CONCLUSIONS: Our data provide evidence that short-term CD154 blockade is insufficient to prevent transplant arteriosclerosis, even in combination with CD8+ T-cell depletion. Moreover, the increased expression of the Th2 cytokine interleukin-4 within the graft may be responsible for the development of transplant arteriosclerosis in the long term.

Animals↗
PubMed2000

CD40-CD40 ligand-independent activation of CD8+ T cells can trigger allograft rejection.

In experimental transplantation, blockade of CD40-CD40 ligand (CD40L) interactions has proved effective at permitting long-term graft survival and has recently been approved for clinical evaluation. We show that CD4+ T cell-mediated rejection is prevented by anti-CD40L mAb therapy but that CD8+ T cells remain fully functional. Furthermore, blocking CD40L interactions has no effect on CD8+ T cell activation, proliferation, differentiation, homing to the target allograft, or cytokine production. We conclude that CD40L is not an important costimulatory molecule for CD8+ T cell activation and that following transplantation donor APC can activate recipient CD8+ T cells directly without first being primed by CD4+ T cells.

Animals↗
PubMed2000

CD8+ T cells contribute to the development of transplant arteriosclerosis despite CD154 blockade.

BACKGROUND: The CD40-CD154 receptor-ligand pair plays a critical role in allograft rejection by mediating the activation of endothelial cells, antigen-presenting cells, and T cells. Blockade of this interaction prevents acute allograft rejection and leads to prolonged allograft survival in numerous experimental models, but in most cases indefinite graft survival is not achieved due to evolving transplant arteriosclerosis. In this study, we have used a model of transplant arteriosclerosis to investigate whether CD4+ and CD8+ T cells are differentially affected by CD154 blockade. METHODS: BALB/c (H2d) aortic grafts were transplanted into C57BL/6 (H2b) recipients treated with anti-CD154 monoclonal antibody in the presence or absence of CD8+ T-cell depletion. Histology and morphometric measurements were performed on day 30 after transplantation. RESULTS: Only combined treatment with anti-CD154 and anti-CD8 monoclonal antibodies resulted in a significant reduction of intimal proliferation (33 +/-10% vs. 67+/-14%; untreated control). Administration of either antibody alone did not produce this effect. Thymectomy did not alter the degree of intimal proliferation observed in any of the treatment groups. CONCLUSIONS: Our data provide direct evidence that CD8+ T cells are not targeted effectively by CD154 blockade and that the transplant arteriosclerosis seen after CD154 blockade is not due to recent thymic emigrant T cells.

Animals↗
PubMed2000

The importance of H2 haplotype sharing in the induction of specific unresponsiveness by pretransplant blood transfusions.

BACKGROUND: The beneficial effect on graft survival achieved by pretransplant blood transfusions is well established. Previous studies have shown that the degree of major histocompatibility complex (MHC) (mis)-match between the transfusion donor and the recipient plays a determining role. However, other factors are also involved. In this study, we explored the hypothesis that, in addition to sharing of MHC antigens between the transfusion donor and the recipient, the MHC type of the organ donor is also of importance. METHODS: To mimic the human situation, F1 mice, rather than inbred strains, were pretreated with haplotype-shared allogeneic whole blood transfusions and transplanted with hearts of organ donors with different matched or mismatched H2 haplotypes. RESULTS: When a heart was transplanted 1 week after donor-specific transfusion (DST; blood transfusion donor=organ donor), an excellent prolongation of graft survival was obtained (median survival time: 77 days vs. 9 days in untreated mice). However, this was only the case when a haplotype was shared with the recipient; a DST given with no match between organ donor (=BT donor) and recipient did not induce any prolongation. Furthermore, in order to obtain the optimal beneficial effect of a haplotype-shared blood transfusion, the other haplotype of the transfusion donor had to be mismatched with the recipient. The immunogenetic studies showed that haplotype-shared blood transfusions in combinations where the H2 type of the organ donor differed from that of the transfusion donor are less efficient in inducing prolongation of graft survival. CONCLUSIONS: These results demonstrate that haplotype-shared blood transfusions can induce a significantly prolonged survival of cardiac allografts in F1 mice. The immunogenetic studies suggest that presentation of alloantigen-derived peptides in the context of self MHC (the indirect pathway of allorecognition) is essential for the beneficial effect of haplotype-shared blood transfusions.

Animals↗