摘要:

Adult male (LewisxBrown Norway) F1(LBNF1) rats received heterotopic small intestinal transplants from Lewis donors. Lewis-to-Lewis and LBNF1-to-LBNF1isografts served as controls. All of the allograft recipients died after a median survival time of 16.2 days, but all isografted rats survived indefinitely. During the period of deterioration, allografted rats developed marked cutaneous erythema and became increasingly weak and cachectic. Histological changes of the skin, spleen, and grafts were characteristic of graft-versus-host disease (GVHD). There was a marked degree of relative splenomegaly. Injection of spleen cells obtained from LBNF1rats with clinical GVHD into the foot-pad of syngeneic LBNF1rats resulted in significant enlargement of the ipsilateral popliteal lymph node. The degree of lymph node enlargement was comparable to that induced in LBNF1rats by injection of normal Lewis spleen cells. These results clearly demonstrate the ability of the small intestinal allograft to cause rapid and fatal GVHD in rats that are incapable of graft rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection.Candidaspecies andTorulopsis glabratawere responsible for 22 episodes andAspergillusspecies for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P<0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P<0.05) and antibiotics (P<0.05), longer transplant operative time (P<0.02), longer posttransplant operative time (P<0.01), duration of antibiotic use after transplant surgery (P<0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P<0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P<0.05). A total of 41% (9/22) ofCandidainfections resolved, but allAspergillusinfections ended in death.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Blood eosinophilia is invariably associated with acute cellular episodes of rejection, characterized by blastogenic inflammation in fine-needle aspiration cytology of the renal transplant. The eosinophilic episode usually precedes the onset of inflammation by 1–4 days and carries no correlation with the intensity of the inflammation. No eosinophilia is present in the blood immediately (within 3 days) after tranplantation or in patients displaying neither clinical nor cytological evidence of rejection. This suggests that the up-regulation of eosinophilia is not related to the transplantation procedure itself or to inflammation, but rather to very early steps in the rejection cascade. A likely possibility is a direct signal from alloactivated T cells. Treatment of rejection with steroids, but not with cyclosporine or, when not treating, rejection, rapidly down-regulates the episode. At present we do not know whether episodes of eosinophilia are also associated with other occasions of T cell activation, like viral infection—therefore the value of eosinophil differential as a diagostic test for rejection cannot be determined.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

This is a report of a patient who underwent cadaveric renal transplantation in spite of the presence of three HLA-A, B and two DR antigen mismatches between the recipient and donor. The recipient received more than 20 units of blood before transplantation. The crossmatch between the recipient's serum and the T and B cells of the donor was negative. The patient exhibited hepatic dysfunction from the early posttransplant period, which eventually led to discontinuation of azathioprine or Bredinin at one year posttransplantation. Thereafter, only betamethasone was administered once every 3 days. The patient has maintained good renal function for more than one year following withdrawal of the immunosuppressants. It appeared that transplantation tolerance was established in this patient. Therefore, we examined the mechanisms sustaining the tolerance. Both nylonwool-adherent, alloantigen-specific suppressor T cells and nonadherent, nonspecific suppressor T cells were observed in the lymphocytes of the patient after transplantation. It was also shown that suppressive antibody was present in the serum directed toward the clone of autologous lymphocytes that reached with the mixed lymphocyte reaction (MLR) antigen of the donor. In the inhibition test against various types of MLR antigens using this suppressive antibody, it was found that the reaction against the donor cells was suppressed when the responding cells shared the same class I antigen with the recipient. When the stimulating cells had the class II antigen of the donor, the reaction of the specific responding cells was also inhibited. These inhibiting effects were only seen when the responding cells were pretreated with the antibody, but not when stimulating cells were pretreated.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Currently the mechanism of renal allograft rejection is not well understood. This study was designed to determine whether induction of monocyte procoagulant activity (MCPA) is important in the pathogenesis of renal allograft rejection. The MPCA assay was performed utilizing a one stage clotting assay both in normal and in factor-VII-deficient plasma. There was no increase in spontaneous MPCA in 20 patients with end-stage renal failure and in 10 patients following abdominal or orthopedic operation, as compared with 20 normal controls. MPCA was assessed daily in 18 patients who had received renal allografts. Rejection episodes (RE) were predicted on the basis of persistent elevation in MPCA as compared with pretransplant levels. Rejection was diagnosed clinically and treated on the basis of standard criteria. Treated RE were compared with those predicted by elevated MFCA, and 3 patients were assessed as having no RE by MPCA and by standard criteria. In 8 RE, MPCA correlated temporally with RE (same day) when compared with standard criteria. In 12 RE, MPCA was predictive of rejection preceding standard criteria by at least 24 hr. There were 7 false-positive predictions on the basis of MPCA; however, there was only 1 false negative. MPCA was shown to be a prothrombinase by its dependence only on prothrombin and fibrinogen for full activity. MPCA may be important in the pathogenesis of allograft rejection, and additionally it may be a useful adjunct in the clinical management of this disease.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

In general, breeding pairs are not major histocompatibility complex (MHC)-compatible, and therefore the fetoplacental unit can be considered as a natural allograft. In many mammals pregnancy leads to the production of nonlytic antibodies of antipaternal MHC specificity. It has been suggested that these protect the semiallogeneic fetus from rejection by acting as blocking or enhancing factors—or, alternatively, that they are part of a humoral response involved in the establishment of normal pregnancy. These hypotheses were tested in allomated mice made B cell deficient by continuous treatment with αIgM$mU antiserum. The status of the maternal immune system was assessed by in vivo antibody production, in vitro mitogen responses, and allograft rejection. By these criteria B cell function could not be demonstrated in αIgM$mU treated female mice, but T cell responses were unaffected. Allogeneic pregnancy, however, was not compromized by this humoral immune system dysfunction—litter size and neonatal survival being the same in the αgM$mU and control serum-treated groups. These results indicate that a maternal humoral immune response is not essential for the establishment of pregnancy or the survival of the semiallogeneic: fetus.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

The mixed lymphocyte kidney culture (MLKC) in humans has been studied in normal and abnormal clinical conditions. Human renal cortical cells were extracted by collagenase treatment from the kidneys of “normal” heart-beating cadaver organ donors (n=13), patients with end-stage renal disease (ESRD) at pretransplant bilateral nephrectomy and splenectomy (n=13), and from irreversibly rejected, renal allografts at the time of graft nephrectomy (n=5). Proliferation of peripheral blood T lymphocytes of 2-DR-mismatched volunteers occurred in response to kidney cortical cells extracted from each of the 3 donor categories in a reaction termed theallogeneic mixed lymphocyte kidney culture.Additionally, splenic T cells from cadavers and patients with ESRD were seen to react to their autologous kidney cells. The renal cortical cells extracted from ESRD kidneys were more stimulatory in the allogeneic and autologous MLKC responses than those extracted from “normal” cadaver kidneys even when the ESRD kidneys were 99% depleted of passenger T and B lymphocytes, by treatment with monoclonal antibodies T11 and B1. In order to help define the antigens operative in the MLKC, we pretreated stimulating lymphocytes and renal cortical cells with anti-class II monoclonal antibodies. The allogeneic mixed lymphocyte reaction and MLKC were inhibited ca. 80% and 30%, respectively. The autologous MLKC was unaffected by this treatment. To further support that tissue-specific immune mechanisms were operative in the reaction, experiments were performed with infiltrating lymphocytes isolated from the ESRD kidneys, which were seen to generate a proliferative response when stimulated with autologous cortical cells. However, the response of these same in filtrating lymphocytes when stimulated with allogeneic lymphocytes (MLR), was markedly weaker than the response of the patients' autologous spleen cells. In addition, two kidneys were obtained at rejection from recipients that had received grafts from HLA-MLR-identical sibling donors. A lymphoproliferative reaction of recipient peripheral blood T lymphocytes occurred in response to (donor) renal cortical cells, but not to donor peripheral blood lymphocytes. In contrast, infiltrating (recipient) kidney lymphocytes responded to the kidney cortical cells and to donor peripheral blood lymphocytes. Moreover, peripheral blood T lymphocytes of the HLA identical donor responded to his own kidney cortical cells, which, were isolated from the rejected recipient kidney, and did not respond to recipient peripheral blood lymphocytes. Finally, a “normal” cadaveric kid ney was fortuitously available at the same time that a rejected transplant (cadaver) was being studied. The recipient and the supplier of the normal kidney were mismatched at both DR loci. Infiltrating lymphocytes from the rejected graft responded more strongly to the 2-DR-mismatched kidney cells than to the spleen cells of the same donor. In contrast, peripheral blood T lymphocytes from the recipient showed a greater response to the 2-DR-mismatched splenocytes than to the corresponding kidney cells. These results provide evidence that “tissue-specific” antigens are operative in the MLKC, with a possible biologic significance in the pathogenesis of end-stage renal disease and the loss of kidney transplants.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Systemic adoptive transfer was employed to assess the immunosuppressive efficacy of antigen-specific suppressor T (Ts) cells purified from recipients treated with 3MKCI-extracted donor histocompatibility antigen (Ag) and cyclosporine (CsA). Suppressor cells were obtained from Wistar-Furth (WFu, RT-1u) hosts treated with a single i.v. injection of 5 mg 3M KCI-extracted donor Buffalo (Buf, RT-1b) antigen combined with a three-day course of CsA, a group that displays prolonged renal allograft survival (MST 23.2±10.2 days) compared with animals treated with CsA alone (MST 12.2±2.4 days). These noncytolytic, OX-8 phenotype, 800-rad-resistant/1500-rad-sensitive, nylon-wool-nonadherent and cyclophosphamide-sensitive suppressor T cells (1x106) were adoptively transferred ten days after transplantation into virgin, secondary syngeneic hosts-thereby prolonging Buf graft survival from 7.2 to 17.5 days. The suppressor effect was immunologically specific; adoptive transfer did not prolong the survival of third-party Brown-Norway (BN) grafts (MST 10.4±3.1 days) compared with the nontreated control group (MST 11.0±2.9 days).The potency of Ts cells purified from Ag-CsA-treated hosts to transfer unresponsiveness into normal secondary WFu hosts (MST 17.5±8.0 days) was stronger than that of Tscells from hosts treated with CsA only (MST 10.6±2.6 days). Moreover, in vitro stimulation of monoclonal-antibody-purified Tscells by irradiated donor Buf spleen cells potentiated the in vivo induced suppressor activity, leading to an MST of 38.1±32.6 days; indeed 3 of 12 animals (25%) displayed permanent unresponsiveness. Furthermore, Tscells from Ag-CsA-treated hosts displayed a synergistic effect with a three-day course of CsA administration into the secondary hosts (MST 24.2±8.0 days) compared with animals only treated with CsA (MST 12.2±2.4 days,P<0.001). Moreover, the combination of the Ag-CsA regimen with Tscells administered one day after transplantation caused even greater prolongation of graft survival (MST 34.2±14.2 days) compared with Ag-CsA-treated hosts (MST 23.2±10.2 days,P<0.025). Thus adoptively transferred antigen-specific suppressor T cells may be explored to intensify the specific immunosuppressive effect of the Ag-CaA regimen to achieve long-term unresponsiveness.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

In a Lewis-BN rat model, the antibody response to transfused blood cells from strongly histoincompatible donors was suppressed by preincubation of blood with specific antidonor antiserum or broadly reactive heterologous antilymphocyte serum (ALS). Suppression was achieved even when excess antiserum was removed by washing prior to injection. The suppressive effect was dose-dependent. Broadly reactive ALS was even more effective than specific antidonor antiserum in inhibiting the primary antibody response. Lewis animals pretreated three times with ALS-coated BN blood showed no secondary antibody response against subsequent BN-blood booster injections. Our experiments may be relevant for the prevention of undesired sensitization to donor-specific transfusions prior to related donor kidney transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

(JxK)F1hybrid frogs,Xenopus laevis, were produced by mating between the MHC-homozygous but distinct “J” and “K” group frogs. When the spleen or splenocytes from parental J were transplanted into the F1frogs, a typical graft-versus-host reaction (GVHR) was induced that included wasting and death, accompanied by a prominent spleen enlargement and other histological changes in skin and lymphoid organs. To induce the reaction, sensitization against F1cells prior to transfer of spleen was necessary. The reaction was accelerated when the parental donor cells had been sensitized by γ-irradiated leukocytes from the F1hybrid. The injection of presensitized triploid J splenocytes into F1hybrids followed by ploidy analyses revealed that the donor cells constituted the major call population in host lymphoid organs—such as the spleen, liver, and kidney-but not the thymus. These observations provide the first clear evidence in poikilothermic vertebrates for GVHR caused by parental lymphocytes.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID