摘要:

Peripheral blood mononuclear leukocytes (cells of marrow donor origin) from 89 patients were collected at various times after allogeneic marrow transplantation, stimulated in vitro by phytohemagglutinin, and assayed for the production of interleukin 2 (IL-2). This was done by testing culture supernatants for their ability to induce proliferation of human lymphoblasts and/or IL-2-dependent cultured murine cytotoxic cells. Supernatants from cultures of patient cells were compared with those of marrow donor cells. Supernatants produced by cells from most short-term marrow recipients (30–101 days postgrafting), regardless of the presence or absence of acute graft-versus-host disease (GVHD), and those from most long-term patients with chronic GVHD (103–1932 days postgrafting) had significantly lower-than-normal IL-2 activity, whereas cells from most long-term marrow recipients without GVHD (353–1934 days postgrafting) had essentially normal IL-2 activity. Additionally, we tested the ability of monocytes from 35 marrow recipients to produce interleukin 1 (IL-1) in response to lipopolysaccharide as compared with monocytes from marrow donors or normal unrelated individuals. IL-1 activity in culture supernatants of patient cells, regardless of the time of testing after marrow grafting and the status of GVHD, was found not to differ from that in supernatants of normal cells. These findings suggest that impaired T cell functions seen in some (but not all) marrow recipients are probably not due to IL-1 but to IL-2 deficiency or to the mechanism that causes IL-2 deficiency.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

A 36-year-old woman with a 26-year history of insulin-dependent diabetes mellitus developed chronic renal failure in 1974 and was started on dialysis. She received a kidney transplant from her HLA-identical brother. Her HLA typing showed the following antigens: A1A28, B8, B12(44), BW4, BW6DR3, and DR4. Nephrectomy performed prior to transplantation showed advanced diffuse diabetic glomerulosclerosis.: Her postoperative course was relatively uncomplicated, but within the next seven years she gradually developed symptoms of deteriorating renal function and hypertension. Two years later, a renal arteriogram showed 90% stenosis of the main renal artery. Biopsy of the kidney was obtained during surgical repair of this lesion and showed diffuse nodular diabetic glomerulosclerosis.: Since the B8/DR3form of diabetes is reported to have a predilection for diabetic microangiopathy and vascular complications, we are speculating that the patient's antigenic composition might have enhanced the recurrence of the diabetic lesions in the transplanted kidney.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

From January 1981 through 1983 80 cadaver donor renal allografts were transplanted at a single center utilizing prospective HLA-DR matching. All patients received at least two blood transfusions prior to transplantation. One year actual allograft survival of 77% for initial grafts and 57% for retransplantation was observed. When there was no DR mismatch the results were 84% and 80% respectively. Only 6% of no-DR-mismatch initial grafts were lost to rejection or patient death. These significantly better results were associated with decreased incidence of acute rejection episodes with transplants well matched for DR. Matching for A and B locus antigens conveyed no benefits in this series. Use of prospective DR matching for donor/recipient selection also resulted in efficient transplantation. Patients receiving initial grafts waited an average of 3.9 months while retransplanted patients waited an average of 13.5 months after being entered on the waiting list. The data suggest that if all transplant centers would preferentially share kidneys regionally on the basis of DR matching, nearly all patients could receive timely allografts with no DR mismatch and good results at one year with conventional immunosuppressive therapy.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Ultraviolet-light-induced murine skin tumors were analyzed for the ability to induce transplantation immunity and cytotoxic lymphocytes in syngeneic mice. A correlation was found between tumor regression and the induction of cytotoxic T cells with specificity for a unique tumor-associated antigen. Processing tumors possessed tumor-associated transplantation antigens (TATA), which could be demonstrated by transplantation in hyperimmunized mice. Progression correlated with a lack of splenic cytotoxic T cell reactivity. High levels of in situ cytotoxic reactivity could be induced by presenting the tumor-specific antigen on nongrowing tumor cells. Tumor-bearer hosts were shown to be sensitized to TATA because cultured tumor-bearer T cells adoptively transferred protection against tumor out-growth. Mechanisms of the in vivo suppression of anti-tumor immunity are discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

The influence of the cellular level of adenosine triphosphate (ATP) in the liver on bile excretion was studied in rats. In ischemia, the cellular ATP level decreased rapidly—and, concomitantly, bile flow stopped within 5 min. Administration of L-ethionine i.p. to rats reduced the bile flow rate with decrease in the cellular ATP level. The correlation between the bile flow rate and the cellular ATP level was confirmed in a liver perfusion system. On anoxic perfusion, the ATP level and bile flow rate changed in the same manner as in ischemia. The recovery rates of both on reoxygenation decreased with increase in the anoxic perfusion period. During perfusion under oxygenated conditions, decrease in cellular ATP to various levels by infusion of various concentrations of potassium cyanide, an inhibitor of respiration, resulted in corresponding and concomitant suppression of bile excretion. Kinetic analysis of the bile flow rate revealed a Michaelis-Menten-type curve for the cellular ATP level. The apparent Kms for ATP of bile flow rate in L-ethionine-treated rat liver and liver perfused with potassium cyanide were 1.0 and 1.6 mM, and their Vmax values were 4.1 and 2.5 μl/min/g liver, respectively. The concentrations of main bile components, such as phospholipids, cholesterol, and taurocholate increased, but their total outputs decreased with decrease in the ATP level, and returned to the normal range with recovery of the ATP level. Thus, it was shown experimentally that the extent of hepatic injury can be assessed simply by monitoring the bile flow rate, which reflects the cellular level of ATP.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

In the rat a single i.v. injection of donor whole blood (0.5 ml) 7 days befor a renal allograft leads to complete suppression of rejection and permanent acceptance of the graft in DA(RT11)-to-LEW(RT11), LEW-to-DA, and (DAxLEW)F1-to-DA combinations. This effect is donor-specific. Purified erythrocyte preparations were used for pretreatment (8x109erythrocytes) 7 days before transplantation in the same strain combinations. The contamination by leukocytes was 1300 per 8x109erythrocytes after one method of preparation, but only 1.3 per 8x109erythrocytes after further purification by affinity chromatography. Both preparations of purified erythrocytes were able to suppress rejection and induce permanent acceptance of an allograft. The role of contaminating leukocytes in the first preparation was further excluded by pretreating rats with 1300 lymphocytes, but in these animals allografts were rejected in the normal fashion. The effect of the erythrocyte pre-treatment was donor-specific, dose-dependent, only effective if given by the i.v. route, and not effective if given less than 7 days before transplantation. Further-more neither lymphocytotoxic nor erythrocyte binding antibody could be detected in rats pretreated with purified erythrocytes. These experiments show convincingly that, in the rat-in the strain combinations tested-pretreatment with erythrocytes, that express cell surface class I MHC antigens, but not class II products, can induce specific suppression of rejection of a renal allograft.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

The influence of exogenous interleukin 2 (IL-2) on the immunosuppressive effect of cyclosporine in the mixed lymphocyte response (MLR) was examined. Results show that addition of exogenous IL-2 to a MLR containing graded doses of CsA (0.01–2.5 μg/ml) restored a normal proliferative response to alloantigens. In contrast, the effect of exogenous IL-2 on the induction of cytotoxic lymphocytes in primary MLR in the presence of CsA was variable. At the highest doses of CsA (0.5–2.5 μg/ml), no cytotoxic T cell activity could be detected, regardless of the presence of exogenous IL-2. However, at a lower dose of CsA (0.1 μg/ml) that routinely resulted in the total inhibition of cytotoxic T cell induction, addition of exogenous IL-2 resulted in significant levels of detectable cytotoxic T cell activity. The effect of time-sequential addition of CsA or CsA-plus-exogenous-IL-2 on the proliferative and CML responses in MLR was also examined. Results show that addition of CsA to ongoing primary MLR cultures within the first 48–96 hr of culture results in the significant inhibition of the proliferative and CML response in MLR. Addition of CsA-plus-exogenous-IL-2 to ongoing cultures resulted in no significant inhibition of the proliferative response. In contrast, addition of CsA-plus-exogenous-IL-2 within the first 4 hr of culture did not overcome the immunosuppressive effect of CsA. At 18 hr of culture addition of CsA resulted in complete suppression of the CML response, whereas the addition of CsA–plus–IL–2 resulted in significant levels of cytotoxicity. Thereafter addition of CsA-plus-IL-2 resulted in enhanced levels of cytotoxic T cell activity compared with cultures receiving CsA alone. Taken together, our results suggest that: (1) exogenous IL-2 can overcome the immunosuppressive effect of CsA on the proliferative response in MLR to alloantigens; (2) at high levels of CsA, IL-2 cannot overcome the immunosuppressive effect of CsA on the induction of cytotoxic T-lymphocytes; (3) there are

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

We have used a variety of standard inbred, recombinant, and congenic rat strains to establish the effect of MHC and non-MHC genetic incompatibilities on bone marrow transplantation. The role of these loci in the successful establishment of bone marrow engraftment was first determined by examining the potential of do-nor marrow to protect recipient rats from a lethal dose of the myeloablative drug busulfan. Similar donor/recipient combinations were then used to examine the effects of the same incompatibilities on the induction of fatal graft-versus-host disease (GVHD) in recipients conditioned with a combination of busulfan and cyclophosphamide. The data obtained indicate that: (1) a difference for the entire MHC of the rat is sufficient to prevent marrow engraftment and to produce fatal GVHD; (2) the class IRT1.Alocus of the rat MHC has a differential effect on bone marrow transplantation, since disparity for this locus prevents successful marrow engraftment, while this gene has little effect on the development of fatal GVHD; (3) disparity for the class IRT1.Elocus has no effect on bone marrow engraftment and does not stimulate GVHD; (4) disparity for the class II locus,RT1.D, can prevent marrow engraftment and elicit fatal GVHD; and (5) incompatibility for non-MHC genes can prevent the establishment of bone marrow engraftment and elicit fatal GVHD.

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1985

数据来源: OVID