摘要:

The survival of semiallogeneic or fully allogeneic rat kidney allografts was prolonged in some strain combinations with immune complexes formed with haptenconjugated alloantigens (TNP-Ag) of donor origin and a mouse monoclonal antihapten antibody (anti-TNP). Complexes were administered i.v. at the time of operation—and, in some cases, on subsequent days. Complexes using TNP-modified alloantigen in various forms—donor whole spleen lymphocytes, cellular membrane sonicate, or papain-solubilized—were all found to be effective in enhancing graft survival in specific donor-recipient combinations. Indefinite survival was obtained in some recipient groups with semiallogenic donors, and a more modest degree of enhancement was seen with fully allogeneic kidneys. The enhancing effect was shown to be donor-specific and highly dependent on the ratio of anti-TNP antibody to TNP alloantigen.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

A short course of procarbazine hydrochloride (PCH; 50 mg/kg) and antilymphocyte serum (ALS; 5 ml/kg), administered to Lewis (LEW;RT11) rats in the first week following transplantation of Brown Norway (BN;RT1n) kidneys, substantially prolonged allograft survival and induced long-term survival in 62% of the grafts. The two agents acted synergistically, in that neither of them administered alone had much effect. Graft recipients did not produce detectable cytotoxic antibodies and antigen-reactive cells injected i.v. were not diverted to the liver, thus showing that neither antibodies nor immune complexes are likely to mediate the unresponsiveness. Spleen cells from graft-bearing recipients failed to cause graft-versus-host responses (GVHR) in both (LEWxBN)F1and (LEWxDA)F1hybrids, but they specifically suppressed the GVHR given by normal syngeneic cells to donor strain (BN) antigens. This suppression was specific because the response against third-party antigens (DA; RTIa) was unaffected. Adoptive transfer of spleen and thymus cells from PCH-ALS-treated LEW rats bearing healthy BN kidneys caused a profound prolongation of BN graft survival in sublethally irradiated LEW recipients. This transfer was specific and mediated by W3/13+(T) lymphocytes. It is concluded that a limited regimen of PCH and ALS given in the first postoperative week incites the generation of specific suppressor T lymphocytes and that this form of immunosuppression, even without preoperative donor antigen, is an effective way of prolonging kidney allograft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Three solutions, hyperosmolar citrate, modified Collins' C2, and Sacks' II solutions were compared as media for cold storage preservation (arterial infusion and subsequent cold storage in the same medium at 0–4 C) of the rat pancreas with a view to preservation of endocrine function. Pancreatic isotransplantation was performed following cold ischemic intervals of 0, 24, 30, and 36 hr, into streptozotocin-induced diabetic recipients. Results were assessed by normoglycemic survival and insulin response, together with K values following i.v. glucose tolerance tests at 3 months postoperatively; 24-hr preservation was achieved with equal success using modified Collins' C2Solution or hyperosmolar citrate—but not with Sacks' II solution. Preservation for 30 hr was consistently successful using modified Collins C2solution only, but the period could not be extended with success to 36 hr. Hypoglycemia and hyperinsulinemia occurred 24 hr postoperatively in the majority of animals receiving grafts stored in Sacks' II solution, but to a much lesser extent using modified Collins' C2and hyperosmolar citrate. This was also temporarily seen in grafts stored for 36 hr in modified Collins C2Solution. At 3 months postoperatively after 30 hr cold ischemia, i.v. glucose tolerance tests showed the hyperosmolar citrate cold-stored grafts had lower K values and significantly reduced insulin responses compared with grafts stored in modified Collins' C2solution. The modified Collins' C2solution proved to be the most effective of the three solutions tested.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The incidence of infection in 86 consecutive patients having bone marrow transplantation for acute or chronic myeloid leukemia, in a protocol in which cyclosporine was the main immunosuppressant, was low. Severe bacterial infections were infrequent and mostly caused by gram-positive cocci but early bacterial infection was often associated with severe graft-versus-host disease. Fungal infections were prevented by nystatin and amphotericin thus avoiding the difficult combination of cyclosporine and ketaconazole. Viral infections were no more common than in other series but, in patients with mismatched grafts, they tended to be associated with neurological complications clinically diagnosed as encephalitis.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Renal allograft tolerant patients show specific unresponsiveness in mixed-lymphocyte culture assays when confronted with donor stimulating cells. Separation of posttransplant peripheral blood lymphocytes into Fe γ+and Fc γ-by rosetting and into OKT8+, OKT8-by cytofluorometry enabled the demonstration of normal responses by Fc γ-and OKT8-cells, whereas the proliferation of OKT8+and Fc γ+cells was depressed specifically in the presence of donor cells. Using mixing experiments, we showed that OKT8+and Fc γ+posttransplant lymphocytes exert a suppressive effect specific to the donor-recipient pair on the proliferative response of the pretransplant lymphocytes.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Acute human renal allograft rejection induces a dramatic elevation of serum amyloid A protein (SAA). To evaluate the clinical significance of this finding we monitored 31 consecutive recipients of cadaveric renal allografts by daily SAA measurements. SAA increased significantly during 37/38 rejection episodes. Mean peak SAA level during the reversible rejections was 271 ± 31 mg/L (SE, median 220 mg/L, n = 35) and during the irreversible rejections 680 ± 29 mg/L (median 705 mg/L, n = 3). Excluding the predictable operation-induced SAA elevations that peaked on the second post-operative day, there were seven out of 42 SAA elevations (100 mg/L) not due to rejection. They were all caused by severe infections, and in one instance by a surgical complication. In 17 of the 35 SAA-positive rejections the SAA elevation (100 mg/L) preceded the clinical diagnosis by 1–5 days; in 11 it occurred on the same day; and in 7 one day later. Rejection episodes in recipients with initially nonfunctioning grafts were all also characterized by significant SAA elevations. We conclude that daily monitoring of SAA concentrations offers a valuable aid in the early diagnosis of acute allograft rejection. The SAA test is not a renal function test, so it can also be carried out in transplant patients who are anuric or oliguric in the postgrafting stage.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The frequency of nephrotoxicity in the absence of identifiable prerenal or postrenal causes within five days of operation in 27 liver transplant recipients was found to be 71% in those treated with i.v. cyclosporine alone, 37.5% with i.m. cyclosporine alone, and 16.7% with prednisolone and azathioprine. Renal failure following i.v. cyclosporine was characterized by an immediate fall in urine output and creatinine clearance with well-preserved tubular function—findings consistent with a reduction in renal blood flow or glomerular filtration rate, or both.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Bone marrow transplant recipients undergo ablation of host immune defenses with total-body irradiation or high dose chemotherapy, or both. Over a 5.6-year period, mycobacterial infections were observed in 7 of 682 patients with leukemia who received marrow grafts. Four patients had pulmonary and three extrapulmonary infection. Granulomas were observed in the lungs of three patients, in the liver of one patient, and in the skin of one patient. Cultures revealedMycobacterium tuberculosisin two patients,Mycobacterium fortuitumin two patients, andMycobacterium kansasiiin one patient. In the six patients treated with antimycobacterial therapy in either the pretransplant or posttransplant period, complete resolution of the infection was achieved. Pretransplant chest radiograph abnormalities suggesting mycobacterial infections should be aggressively evaluated in these immunocompromised hosts. Prophylaxis should be considered in marrow graft recipients with a well-established history of inadequately treated tuberculosis, previous Bacille Calmette-Guerin immunotherapy, known family contacts, recent skin test conversion, or past skin test positivity.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

We have investigated the possibility that nonspecific cytotoxicity may be involved in the pathogenesis of the intestinal phase of the graft-versus-host reaction (GVHR) in mice. A GVHR was induced in unirradiated (CBAxBALB/c)F1mice and natural killer (NK) cell activity against YAC-1 followed in the spleen, mesenteric lymph node (MLN), and isolated intraepithelial lymphocytes (IEL). Augmented NK activity developed simultaneously in all tissues in parallel with the progress of the GVHR. The NK activity of IEL also showed a close association with the increased numbers of IEL found on sections of small intestine. Mature T lymphocytes and macrophages did not contribute to the nonspecific cytotoxicity, and antihost cytotoxic T cells were not detected in any tissue.The results indicate that generalized recruitment of NK cells occurs during the GVHR both in peripheral and intestinal lymphoid tissues, and we propose that lymphokines are responsible for this phenomenon. NK cells recruited by a delayed-type hypersensitivity reaction may contribute to the pathogenesis of the GVHR, but an alternative explanation is that NK cells may inhibit the progression of the GVHR.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

B6AF1(H-2KbkDbd) mice were transfused weekly with 0. 1 ml of whole blood from DBA/2 (H-2d) mice. One week after each transfusion, spleen and serum samples were collected. Blood transfusions did not induce blood donor alloantigen-specific cytotoxic T lymphocytes (CTL) in spleens of B6AF1mice. When spleen cells from transfused mice were sensitized to alloantigens in mixed lymphocyte culture in vitro, it was observed that 1–3 transfusions induced suppression of blood donor-specific CTL activity. No suppression of CTL activity was found after 4 transfusions. The cell-mixing experiments demonstrated that the suppression of CTL activity following initial 2 blood transfusions was due to the presence of suppressor cells. The presence of antibodies in sera of transfused B6AF1mice capable of inhibiting CTL was investigated using the CTL-inhibition test. In these experiments, cytotoxic T lymphoblasts generated in MLC in vitro by culturing normal B6AF1spleen cells with x-irradiated DBA/2 cells were treated with serum before testing them for cytotoxicity. The antibodies capable of inhibiting CTL responses were demonstrable in sera from transfused mice. Three and four BT sera caused significant inhibition of CTL responses. The CTL-inhibitory antibodies were specific for effector cells of the B6AF1mice and for target cells of the blood donor DBA/ 2 mice. These results suggest that the inhibition of CTL responses is caused by antibodies directed against the recognition sites on effector T lymphocytes. The data from this study, therefore, demonstrate that BT cause suppression of the recipient's CTL responses against alloantigens present on the blood donor, and that this suppression is mediated by suppressor cells after the initial 1 to 2 transfusions and by antibodies directed against the CTL antigen-specific receptors after subsequent transfusions.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID