Cyclosporine-induced transplantation unresponsiveness in rat cardiac allograft recipients: in vitro determination of helper and suppressor activity.

Lymphocytes from spleen, peripheral blood, thymus, and lymph node of naive rats, nonimmunosuppressed recipients of MHC-incompatible heart grafts, and cyclosporine-treated recipients of MHC-incompatible heart grafts were tested for their ability to augment or suppress proliferation of naive cells in an in vitro MLR co-culture assay. Rats treated with cyclosporine for only 7 days maintained their grafts indefinitely. Potent suppressor activity was found in the peripheral blood and spleen of adult naive rats.

Phenotype, activation status, and suppressor activity of host lymphocytes during acute rejection and after cyclosporine-induced unresponsiveness of rat cardiac allografts.

Serial changes in phenotype, cell cycle, and functional behavior of lymphocyte subpopulations occurring both during acute rejection in unmodified hosts and in long-surviving heterotopic cardiac allografts in rats treated with cyclosporine (CsA) were studied. Using flow cytometry, RNA and DNA content of cells was examined during various phases of cell activation. In animals acutely rejecting their grafts, numbers of cells infiltrating the grafts and in host spleen in G1 phase (higher RNA content) increased, starting from day 3, and peaked by 5-6 days posttransplantation, and numbers of cells in S/G2/M phase (higher DNA content) remained stable.

Vascular access for hemodialysis. Patency rates and results of revision.

Over a 4-year interval, 324 arteriovenous conduits were created in 256 patients with end-stage renal disease as access for chronic hemodialysis. These included 154 Cimino fistulae, 163 polytetrafluoroethylene (PTFE) grafts, and seven miscellaneous grafts. Satisfactory patency rates were demonstrated for as long as 4 years for both Cimino fistulae and PTFE grafts by life-table analysis.

Stability of renal allograft recipients after conversion from cyclosporine to azathioprine.

Forty-eight patients with stable renal function after allotransplantation have been converted from CsA/prednisone to azathioprine/prednisone to assess the short- and long-term effects upon renal function. Virtually all patients show an initial improvement in serum creatinine levels. Three patients developed chronic renal failure after 12 to 21 months, and three died of pneumonia 7, 12, and 19 months later.

Host-graft relationship: the systemic nature of allograft rejection.

The interdependence between immunologic events occurring within acutely rejecting rat cardiac allografts and those in host lymphoid tissues were studied. To evaluate cellular dynamics of allograft infiltration, 111In-labeled thoracic duct lymphocytes from Lewis rats were administered intravenously daily (0 to 7 days after transplantation) to (Lewis X BN)F1 heart-grafted unmodified Lewis rats, sacrificed 24 hours later. Accumulation of thoracic duct lymphocytes in the allografts peaked 4 to 5 days after transplantation.

The potential use of cyclosporine in reconstructive surgery.

Cyclosporine, the first of a new generation of selective immunosuppressive agents, has already proved to be of exceptional value in human organ transplantation; however, its role in human reconstructive surgery remains to be established. The possibility that short-term treatment could be sufficient for indefinite survival of bone, muscle, nerve, and vein allografts is attractive and might provoke changes in prevailing attitudes regarding the use of allogenous tissues in reconstructive procedures. Cyclosporine may start a new line of immunosuppressive agents with more potent therapeutic effect and less potential toxicity.

Kallikrein excretion in renal transplant recipients and in uninephrectomized donors.

The rate of tissue kallikrein (EC 3.4.21.

Clinical experience with cyclosporine and azathioprine at Brigham and Women's Hospital.

Cyclosporine (CsA) immunosuppressive therapy of renal allograft recipients at Brigham and Women's Hospital yielded a 20% increase in 12- and 24-month allograft survival over azathioprine (Aza) treated controls. A trend towards increased allograft survival with better HLA-A,B, or DR matching in recipients of cadaver allografts treated with CsA was appreciated, but it fell short of statistical significance. Nephrotoxicity is common in CsA-treated patients and is manifested by a largely reversible increase in the serum creatinine.

Behavior of helper T lymphocytes in cyclosporine-mediated long-term graft acceptance in the rat.

(LEW X BN)F1 cardiac allografts are rejected acutely (7 days) in unmodified LEW rats, yet survive indefinitely following cyclosporine (CsA) treatment (15 mg/kg im for 7 days) or in T-cell-deprived (B) recipients. Using these models, the function of T helper cells (Th) in the maintenance phase of CsA-mediated long-term graft survival was examined. With monoclonal antibody immunoaffinity fractionation techniques, Th (W3/25+OX8-) were separated from spleens of CsA-treated hosts 3-4 weeks after grafting (CsA-Th), from specifically sensitized (s-Th), or from normal ungrafted (n-Th) rats.

Use of an ectopic pelvic donor kidney for transplantation.

A case is presented in which an ectopic but otherwise normally functioning kidney was used for living related renal transplantation. The donor evaluation was complicated by nonvisualization of the ectopic kidney on intravenous pyelogram, presumably through an error in radiologic technique. Donor nephrectomy and transplantation of the recipient were performed uneventfully; the kidney had an ectopic arterial supply from the donor internal iliac artery which had to be anastomosed to the distal external iliac artery of the recipient because of the short vessels and short ureter.

Conversion from cyclosporine to azathioprine in renal allograft recipients.

Fifty seven recipients of renal allografts initially treated with CsA and low-dose prednisone were switched to azathioprine and low-dose steroids. Ten had prolonged (greater than 28 days) allograft nonfunction after transplantation (group 1), 8 had ongoing, poorly controlled rejection (group 2), and 39 had stable functioning grafts (group 3). With a mean follow-up period of 5 +/- 3 months after conversion, 50 grafts remained functional including 6 of 10 in group 1, 6 of 8 in group 2, and 38 of 39 in group 3.

Experience with cyclosporine and steroids in clinical renal transplantation.

We have reviewed the results of patient survival and transplant function of the last 100 recipients of renal allografts treated with cyclosporine (CyA) plus low-dose steroids since November 1981; the follow-up varies between 3 months and 2 years. A group of 56 individuals transplanted between January 1980 and October 1982 and immunosuppressed with azathioprine (Aza) and steroids were used as comparison. There were five deaths among 100 patients treated with CyA and two among 56 treated with Aza.

Cyclosporine: a new immunosuppressive agent for organ transplantation.

Cyclosporine, a cyclic endecapeptide of fungal origin, has recently been released for use in clinical transplantation. Trials in kidney, heart, liver and bone marrow recipients were encouraging: 1-year graft survival rates were 70% to 80% for kidney and heart recipients, and 60% to 65% for liver allograft recipients. Cyclosporine is also effective in treating bone marrow recipients with acute graft-versus-host disease.

Cyclosporine therapy of rat heart allograft recipients and release of interleukins (IL 1, IL 2, IL 3): a role for IL 3 in graft tolerance?

LEW rat recipients of (LEW X BN)F1 strain heterotopic cardiac transplants treated with cyclosporine A (CsA) (15 mg/kg/day intramuscularly, 7 days) retain grafts indefinitely despite drug withdrawal. Donor-specific suppressor T cells that are active in passive transfer experiments have been harvested from long-term CsA-treated hosts. Although CsA is known to inhibit in vitro cytokine release, the in vivo effects of the CsA on the lymphokine cascade are not known.

Small intestine transplantation in the rat--immunology and function.

Heterotopic, vascularized small intestine transplants were performed in inbred strains of rats to investigate the structural, functional, and immunologic consequences of intestinal transplantation with and without immunosuppression with cyclosporine (CyA). Lewis X Brown Norway F1 intestine was rejected by untreated Lewis recipients in 7 to 10 days. Structurally, rejected intestine was characterized by shortened crypts and villi lined by damaged attenuated epithelial cells.

Interactions between T lymphocyte subsets supported by interleukin 2-rich lymphokines produce acute rejection of vascularized cardiac allografts in T cell deprived rats.

A series of adoptive transfer studies were performed to define both the role of lymphocyte subpopulations and of lymphokines in the reestablishment of immunologic responsiveness towards vascularized organ allografts in T cell-deprived B rats. Acute rejection of otherwise indefinitely surviving cardiac allografts (10.9 +/- 2.

Restoration of allograft responsiveness in B rats. IV. The divergent migratory behavior of lymphocyte populations mediating cardiac allograft rejection.

The T lymphocyte-deprived (B) rat, produced by X-radiation and bone marrow reconstitution of adolescent thymectomized animals, exhibits a true immunological deficit and are unable to reject histoincompatible heterotopic cardiac allografts. A comprehensive survey of lymphocyte traffic in B recipients was performed to correlate the differential potency of specifically sensitized lymphocyte populations mediating re-establishment of immune responsiveness toward the graft, with their migratory and recirculatory behavior. 111In-oxine-labeled thoracic duct lymphocytes (TDL) were retained in the peripheral blood and migrated from nonlymphoid organs to lymph nodes of B recipients in higher proportion than any other lymphoid population, particularly splenic lymphocytes (SL).

Renal artery stenosis in transplant patients.

Although hypertension appears not infrequently among recipients of kidney transplants, renal artery stenosis is relatively rare as a causative factor. A 23-year experience of patients receiving kidney grafts at the Brigham and Women's Hospital was reviewed to ascertain the incidence of renal artery stenosis and its surgical management. Risk factors leading to the condition and selection of patients for operation are emphasized.

Comparison of kidney transplant survival between patients treated with cyclosporine and those treated with azathioprine and antithymocyte globulin.

One hundred thirty two patients who received cadaver kidney transplants in three Boston transplant centers were analyzed to demonstrate the immunosuppressive effect of cyclosporine and steroid therapy versus conventional immunosuppression. Of these, 35 patients received the cyclosporine and steroid regimen and 97 received conventional immunosuppression. The number of patients with preformed reactive antibody was greater in the cyclosporine group; however, a greater number of patients were diabetic in the conventional group.