摘要:

A model for immediate vascularization of skin was devised to examine one of the possible explanations for the differential survival rates of transplants of freely grafted skin and organs, i.e., the increased vulnerability of skin to early ischemic necrosis prior to revascularization. Female Fischer (F) rat skin was transplanted beneath the kidney capsule of tolerant female Lewis (LEW) recipients. This skin healed in and initially appeared to be normal grossly and microscopically. In 27 rats, after 30 days, the composite grafts were excised, and immediately transplanted by means of vascular anastomosis into normal LEW recipients (syngeneic to the kidney portion of the graft and allogeneic to the skin). For 5 days after transplantation of the composite graft, the skin appeared to be normal with minimal or no inflammation in a panel of 11 recipients. From the 6th to 11th day, an active rejection reaction developed at the skin-kidney interface in a panel of six rats. In 10 rats, in which the composite grafts remained in their secondary hosts for 12 to 21 days, rejection of the skin was complete. The renal portion of all composite grafts appeared to be normal histologically. All recipients of composite grafts rejected subsequent orthotopic F skin grafts in an accelerated manner, with median survival times of 8.2 ± 0.3 days compared to 11.5 ± 0.7 days in untreated F LEW controls, demonstrating that the skin on the composite graft was fully immunogenic. These results demonstrate that immediately vascularized skin allografts between rats compatible at the majorAg-B1locus will still be rejected within 2 weeks compared to survivals of up to 48 weeks in renal allografts in the same histocompatibility combination, suggesting that anatomical factors are not sufficient to account for the differences in survival times between skin and solid organs.It has been demonstrated by a number of workers (1–5) that tissues from the same donor may behave differently in their susceptibility to rejection when transplanted as allografts to a given recipient strain, i.e., it appears that tissues and organs are not equally vulnerable to transplantation immunity. This is clearly evident from the work of White et al. (6), who showed significantly prolonged survival of F rat kidney allografts in LEW recipients (>48 weeks) compared to the survival rates of skin grafts in the same strain combination (10.3 days). Pettirossi et al. (7) have determined similar differential survivals of various organ allografts across the same histocompatibility barrier, noting that one-third of the kidneys grafted from (BN X LEW) F! hybrid rats survived from 32 to 71 days in parental strain (LEW) recipients compared to skin graft survivals of 9.1 days. Longer survival times, but not as dramatically prolonged as renal allograft survival times, were seen for heart and pancreas grafts by the same workers. Furthermore, Barker and Bil-lingham (1) using Ag-B-compatible donors and recipients noted survival times as long as 100 days for cardiac allografts compared to skin survivals of 13.8 days. Using backcross animals, they also noted prolonged survival of cardiac allografts as compared with skin from (F X LEW)F1X LEW R2in LEW recipients, suggesting that heart transplants across a spectrum of histocompatibility barriers other than Ag-B are less vulnerable to rejection than skin grafts but apparently more susceptible than kidney allografts.These reports and others (8–10) demonstrate that skin allograft survival does not necessarily dictate the duration of survival of allografts of other tissues. Various explanations for these observations include qualitative and/or quantitative differences in the antigenicity of skin and other organs(11–14),a different intrinsic vulnerability to the immune attack(I, 15),differences in the routes by which antigenic material first “informs” the host of its presence(16, 17),and the difference in lymphatic vascular supply of the allograft(18),the lymphatics being a primary pathway for sensitization by skin but not solid organ grafts(19). Finally, the capacity of the grafted tissue to withstand ischemia may be influential, since areas of necrosis and inflammation may facilitate the release of antigenic material and the accumulation of acute inflammatory cells, possibly potentiating the immune reflex(20, 21). The following experiment was undertaken to evaluate the contribution of the route of sensitization, and the nature of the revascularization to the differential survival rates of skin and renal grafts. A model was devised for the immediate revascularization of skin, thus avoiding the 2− to 4-day period of relative ischemia required for the healing via neovascularization of conventional grafts(22).

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

This study investigated the influence of the administration of pharmacological agents on the recovery of rabbit kidneys from the effects of 1 hr of in situ normothermic ischemia, utilizing acute and chronic models. The agents tested included the diuretics mannitol and furosemide, the vasoactive agents phenoxybenzamine, propranolol, and dopamine, and the membrane stabilizers chlorpromazine and methylprednisolone. A beneficial effect was detected only with the diuretic agents and propranolol when given prior to the ischemic insult.In cadaveric kidney transplantation, normothermic ischemia is known to have a particularly adverse effect on renal function(1–4). In order to protect the kidney from both this and subsequent preservational injury, it is common practice to administer pharmacological agents singly or in combination to both donors and recipients(5–7). Many reports exist advocating the use of individual substances, but the lack of comparative experimental data makes it difficult for the clinician to determine which of these is the most effective. Accordingly, this study was undertaken to compare several of the most widely used agents in a small animal experimental model in which 1 hr of normothermic ischemia served as the test injury.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Kidney transplantations were performed in unrelated, immunosuppressed rhesus monkeys matched for two DR antigens and given five pretransplant transfusions of whole blood. The host-donor combinations were either reactive or nonreactive in mixed lymphocyte culture (MLC) and shared up to three A and B locus antigens with their blood and kidney donors. Although previous monkey experiments had shown a definite positive influence of DR matching as well as of pretransplant transfusions on graft survival, this was not found in the current experiments (the mean survival time for the MLC responsive group was 21.3 days, for the MLC nonresponsive group 28.2 days). It appears therefore that the combination of pretransplant transfusions and matching for DR antigens does not have an additive or synergistic effect on graft survival. In fact, the prominent transfusion effect demonstrated previously may have been somehow compromised by matching for DR antigens. Alternatively, the clearly positive effect of matching for two DR antigens may have been reduced or lost as a consequence of giving the blood transfusions.Two recent developments have had a major impact on clinical and experimental transplantation immunology. The first is that it has been shown that multiple blood transfusions given before transplantation can substantially prolong kidney allograft survival (reviewed in Ref.1). The second is that protection of allografts may be achieved by matching host-donor combinations for the products of theDlocus and the closely associated or identicalDRlocus (reviewed in Ref.2). Both approaches to the prolongation of kidney allografts have been investigated prospectively in rhesus monkeys. First, it was shown that the administration of blood transfusions before transplantation leads to a considerable improvement of graft prognosis(3, 4). It was subsequently demonstrated that matching unrelated monkeys for DR antigens leads to a significant prolongation of kidney graft survival, at least if recipient lymphocytes are MLC negative against kidney donor cells (5). In view of those results, it was clearly of interest to investigate whether matching for DR antigens combined with pretransplant transfusions would show an additive or even synergistic effect on graft survival.In the current experiments, kidney transplantations were performed between unrelated immunosuppressed rhesus monkeys that shared two DR antigens but were also given five blood transfusions before transplantation. The host-donor combinations were either reactive or nonreactive in MLC and shared up to threeAandBlocus antigens with their blood donors as well as their kidney donors. The results were difficult to interpret because, in comparison with controls, no significantly prolonged mean survival times were obtained in the MLR-positive or in the MLR-negative combinations. A number of mechanisms are postulated to explain these unexpected results; they are discussed in the light of the clearly favorable results published previously for recipients which were either matched with their donors for DR antigens (5) or unmatched for DR but given pretransplant transfusions(4).

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Purified rat red blood cells, which express the A region antigens of the major histocompatibility complex (MHC) with which anti-RT-1 (H-l; Ag-B) haemagglutinins combine, fail to stimulate the production of either haemagglutinating antibodies or cellular immunity in allogeneic hosts. Allogeneic red blood cells may in appropriate circumstances be mildly immunosuppressive. Intraperitoneally injected allogeneic red blood cells persist in the host circulation for several weeks. The immune response to skin allografts does not accelerate the destruction of circulating donor strain red blood cells, although the administration of alloantiserum with a high haemagglutinin titre can do so. The manner in which allogeneic red blood cells effect immunosuppression is unknown. Approximately 75% of the red blood cells administered i.v. to nonimmune allogeneic hosts are destroyed, by mechanisms unknown, during the first 6 days after injection. By contrast, about one-half of this number of red blood cells are destroyed by syngeneic hosts during the same period.Red blood cells and platelets in rodents are probably similar in expressing A region (rats) or K-D region (mice) antigens of the MHC, in being nonimmunogenic by themselves and in their capacity for effecting limited immunosuppression. If human platelets have similar attributes, the administration of platelets bearing the appropriate HLA-A, B, and C antigens might be a useful adjunct to conventional immunosuppression in the management of allografts in man. Likewise, the platelet component of blood transfusions might account for their beneficial effect in some renal allograft recipients.Allografts that are incompatible with their hosts in respect to MHC antigens usually stimulate the production of haemagglutinating antibody in rats (1, 2). On the basis of two recombinants (3, 4) the rat MHC has tentatively been divided into two regions, A and B (5). The A region determines erythrocyte and lymphocyte alloantigens and is only weakly stimulatory in the mixed lymphocyte reaction. It appears to be the homologue of the K and D regions of the mouse H-2 complex. The B region contains at least twoIrgenes and also determines lymphocyte alloantigens that are possibly confined to B lymphocytes. There is no evidence that the B region determines red blood cell antigens. This communication records that A region antigens on red blood cells, although targets for haemagglutinating antibodies, fail to stimulate haemagglutinin production. Additionally, in appropriate circumstances allogeneic red blood cells may be immunosuppressive.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

A modified cytotoxicity assay was adapted from classical erythrocytolytic assays, in which complement components were added in sequence to antibody-sensitized cells.This assay was applied to a model system in which mouse sarcoma cells were sensitized with H-2 alloantibody. The stepwise presentation of complement components combined with the stabilization of C2 by iodine treatment considerably augmented the lytic efficiency of human complement. More generally, the techniques adopted for this study provide a new model for obtaining basic information about selective reaction steps concerned in lysis of nucleated cells by alloantibody and complement.Comparisons of the lysis of sheep erythrocytes by xenoantibody with the lysis of mouse sarcoma cells by H-2 alloantibody, in our assay system with oxidized or untreated human complement, disclosed a difference in the kinetics of C142 formation, manifest in a lag phase and a protracted tmaxfor the sarcoma cells. These data may suggest that multiple complement-mediated functional lesions are necessary for immune lysis of nucleated cells.Selective lysis of nucleated cells by antibody and complement has become an indispensable tool for investigating cell surface antigens that characterize sets of lymphocytes with distinct functions(1). The delineation and analysis of several systems of cell surface antigens, such as the Lyt(2, 3)and Lyb(4, 5)series, depends critically on the sensitivity of the cytotoxic assay.Repeatedly, in the past, improvements of complementation in the cytotoxicity assay have come from a better understanding of the factors involved in the complement-mediated lysis of nucleated cells(6). There is abundant information on mechanisms of complement activation and function in hemolytic systems (7) but much less is known of the role of complement in the lysis of nucleated cells(8–14). In particular, no comparative study on reaction sequence and contribution of isolated complement components for nucleated cell lysis is so far available. We show here that lysis of nucleated cells by H-2 antibody can be markedly increased by the use of chemically treated complement(15)in an appropriately modified cytotoxicity assay, presenting complement components in sequence. In addition, we present new basic information about sequential steps of complement binding and activation as these affect nucleated cell lysis in comparison with the classical reaction sequence in erythrocytolysis.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID