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H Ekberg

Publications and source records attributed to H Ekberg.

At least 37 records · Page 2Linked to original sources
PubMed1999

Malononitrilamides and tacrolimus additively prevent acute rejection in rat cardiac allografts.

The novel immunosuppressive agents malononitrilamides (MNA) 279 and 715 are derivatives of A77 1726, the primary metabolite of leflunomide. The effects of these agents have been previously demonstrated in rat skin and cardiac allo- and xenotransplant models. The aim of this study was to evaluate the combination of MNA and tacrolimus in a high-responder rat cardiac allotransplant model. Graft survival was evaluated following 10 days of post-transplant oral therapy of MNA or tacrolimus alone and the drugs combined in PVG recipients of DA grafts. An iso-effect curve of single and combined drugs was constructed. Histological changes in grafts were evaluated at 10 days. MNA (20 mg/kg) or tacrolimus (2.4 mg/kg) alone prolonged graft survival with median survival of 14 and 13.5 days, respectively. Combined therapy of MNA (10 mg/kg) and tacrolimus 1.6 mg/kg likewise resulted in a median survival of 13.25 days and an iso-effect curve for these doses was constructed. Another iso-effect curve for median graft survival of 18-19 days, including MNA (10 mg/kg) + tacrolimus (3.2 mg/kg) in combination, MNA (30 mg/kg) alone and tacrolimus (4.8 mg/kg) alone, was constructed and both isoboles showed a straight line, demonstrating additive effects (zero interaction). In addition, histological analysis of grafts confirmed the benefit of the drug combination. No additional toxicity was noted with combined therapy. Optimal doses of MNA or tacrolimus had comparative effects on graft survival and histological changes, and a combination of the two drugs was beneficial with respect to both these parameters. The iso-effect curves verified additive effects of the drug combination.

Alkynes↗
PubMed1999

Antithymocyte globulin and cyclosporin A are synergistic in an experimental transplantation tolerance model in the rat.

The aim of the present investigation was to study the possible synergistic effect between cyclosporin A (CsA) and antithymocyte globulin (ATG), using the potent immunostimulator, Linomide. DA rats were transplanted with a PVG/c heart to the neck vessels, and the recipients were treated for 10 days with oral CsA (10mg/kg), oral Linomide (160mg/kg) and/or ATG, which was given as a single dose of either 0.02 ml, 0.1 ml or 0.2 ml prior to transplantation. Rats given a combination of ATG and Linomide or CsA and Linomide were used as controls. Synergism between CsA and ATG was tested using the two immunosuppressive drugs given in combination in order to override the challenge of Linomide. CsA or ATG treatment alone resulted in rats with long-term surviving grafts. Addition of Linomide to CsA-treated recipients was followed by early graft rejection. Similarily, Linomide triggered rejection in rats given a low dose of ATG and in recipients given a high dose of ATG if Linomide treatment was prolonged to 21 days. The combination of ATG, CsA and 21 days of Linomide resulted in a significantly prolonged graft survival compared with either ATG + Linomide or CsA + Linomide. These findings demonstrate the synergistic capacity of ATG and CsA in combined immunosuppressive therapy.

Adjuvants, Immunologic↗
PubMed1999

Tolerance or rejection: A delicate balance as judged by exposure of heart-transplanted rats to the immunomodulator Linomide.

When applied in rodent transplant models most immunosuppressive drugs yield adequate graft protection for as long as the drug is given, and permanent graft survival is often induced. The immunomodulator, Linomide, previously shown to stimulate T cells and prevent apoptosis, usually reduces or abolishes both tolerance induction and the graft-protective effect of the immunosuppressive drug. By chance, we observed that Linomide alone exerted a modest but unequivocal graft-protective effect in the BN to WF strain combination. This finding was analysed by simple genetic mapping of rat strains. Untreated WF recipients kept BN grafts for a median of 8 days, whereas Linomide treatment prolonged graft survival to 12. 5 days (P = 0.0001). In control groups (DA to LEW, BN to LEW, DA to WF and WF to BN), median graft survival was 5.5-7 days irrespective of whether Linomide was given. However, the BN to F1 (LEW x WF) combination also manifested slightly longer graft survival in the presence of Linomide. F1 (BN x WF) to WF grafts survived a median of 15 days without Linomide and 46 days with Linomide treatment. Both in the presence and absence of Linomide, two of the control graft combinations [F1 (BN x DA) to WF and F1 (BN x WF) to BN] manifested 6-7-day graft survival. Taken together, our results suggest a delicate balance between unresponsiveness and rejection, while a single agent (Linomide) may either cause on its own long-term survival of allografts in one setting or rejection despite optimal immunosuppression in another setting.

Adjuvants, Immunologic↗
PubMed1999

Presence of arteriovenous shunting in transplanted but not in native single kidney in the rat.

OBJECTIVE: We previously reported the presence of renal arteriovenous (A-V) shunting in rats subjected to renal transplant rejection, hydronephrosis and severe hypotension caused by bleeding. The question as to whether blood partially by-passes the renal cortex under certain conditions is still controversial and an alternative explanation for the findings has been vasodilatation. The aim of this investigation was to determine whether A-V shunting is part of the haemodynamic changes taking place after unilateral nephrectomy and if the sympathetic nervous system is involved. MATERIAL AND METHODS: Unilateral nephrectomy was performed and radioactive microspheres (15.5 microm) were injected into the right remaining renal artery 30 min (n = 10), 24 h (n = 13) and 3 weeks (n = 14) later. The proportion of radioactivity in the lungs was considered to reflect A-V shunting in the kidney. Sham-operated animals (n = 30) and animals (n = 10) without previous sham operation, all with two kidneys, were used as controls. Isogenic renal transplantation (n = 10) was performed after bilateral nephrectomy to represent a denervated single kidney status. RESULTS: Renal A-V shunting was significantly (p < 0.001) reduced 30 min and 3 weeks after unilateral nephrectomy compared with controls. In isogenically transplanted rats, A-V shunting was not reduced compared with sham-operated animals, and significantly (p < 0.001) greater compared with the reduced levels of shunting at all times after unilateral nephrectomy. CONCLUSIONS: Reduced renal shunting of microspheres was observed after uninephrectomy and seems to require an intact renal innervation. It is likely that vasodilatation after unilateral nephrectomy and A-V shunting are two separate phenomena.

Animals↗
PubMed1999

Increased prevalence of apolipoprotein E3/E4 genotype among Swedish renal transplant recipients.

There is increasing evidence that lipoproteins are involved in the progression of kidney diseases and in the deterioration of kidney transplant function, although the exact mechanism is still not known. Common polymorphisms of apolipoprotein E genotype associate with the variability of lipoprotein levels and composition. We have, therefore, determined the apolipoprotein E genotype in a group of 112 renal transplant patients, of whom 27 had had an episode of acute vascular rejection, while 85 had not. We found no difference in apolipoprotein E genotype distribution or in relative allele frequency in the vascular rejection group as compared with the group without vascular rejection. The apolipoprotein E genotype distribution in the transplant group was also compared with that in a group of 407 healthy Swedish individuals. The E3/E4 genotype occurred with a significantly increased frequency in the transplant group: 38.3 versus 16% in the control group (p < 0.001). The prevalence of individuals carrying the epsilon4 allele among the transplant group was also significantly higher (44%) as compared with the control group (30%; p < 0.01). This increase was entirely due to the predominant increase of E3/E4, as the E4/E4 genotype was less frequent in transplant recipients than in normal controls (3.5 vs. 10.6%; p < 0.05). The relative frequencies of epsilon2 (0.044), epsilon3 (0.716), and epsilon4 (0.238) alleles in the renal transplant group were not different from those of normal controls (0. 078, 0.718, and 0.202, respectively). With regard to the prevalence of E4/E4 in the two groups, the lack of difference in the relative frequency of the epsilon4 allele must be interpreted with caution. The results thus suggest that the E3/E4 genotype may be associated with the progression of kidney disease leading to renal insufficiency. However, the apolipoprotein E genotype does not seem to influence the risk of vascular rejection among transplant recipients.

Adult↗
PubMed1998

Activation of donor-specific CTL in a tolerant recipient of cardiac allograft.

Permanent graft acceptance was induced with cyclosporine A in a low responder rat strain combination PVG (RT1(c)) to DA (RT1(av1)) of cardiac transplants. Challenge (alloimmunization) with donor and third-party WF (RT1(u)) cells was performed and followed by the analysis of alloreactive cytotoxicity. The cytotoxic T lymphocytes (CTL) from recipients with permanently accepted cardiac grafts manifested cytolytic activity against third-party target cells but not against donor target cells. The findings demonstrated unresponsiveness to be donor-specific, i.e., transplant tolerance was present. This was verified by retransplantation of the DA recipient with either a second PVG heart (which was accepted) or a third-party (WF) heart (which was rejected). Restoration of donor-specific CTL after injection of exogeneous interleukin(IL)-2 concomitant with challenge showed that the donor-specific CTL were not depleted, but unable to be activated as a consequence of IL-2 deficiency. Despite donor-specific CTL activation in vivo the recipients failed to reject their established grafts, implying an ongoing presence of suppression.

Animals↗
PubMed1998

Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group.

BACKGROUND: Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation. METHODS: We administered daclizumab (1.0 mg per kilogram of body weight) or placebo intravenously before transplantation and once every other week afterward, for a total of five doses, to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine, azathioprine, and prednisone. The patients were followed at regular intervals for 12 months. The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation. RESULTS: Of the 126 patients given daclizumab, 28 (22 percent) had biopsy-confirmed episodes of acute rejection, as compared with 47 of the 134 patients (35 percent) who received placebo (P=0.03). Graft survival at 12 months was 95 percent in the daclizumab-treated patients, as compared with 90 percent in the patients given placebo (P=0.08). The patients given daclizumab did not have any adverse reactions to the drug, and at six months, there were no significant differences between the two groups with respect to infectious complications or cancers. The serum half-life of daclizumab was 20 days, and its administration resulted in prolonged saturation of interleukin-2alpha receptors on circulating lymphocytes. CONCLUSIONS: Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients.

Acute Disease↗
PubMed1998

Malononitrilamides 715 and 279 prevent accelerated cardiac allograft rejection synergistically with cyclosporin A in presensitized rats.

A77 1726 is a malononitrilarnide (MNA) and the active metabolite of leflunomide. Leflunomide has been extensively investigated and shown to be a potent immunosuppressive drug. However, the half-life of A77 1726 is about 15-18 days in humans and the leflunomide is, therefore, currently being evaluated for the treatment of autoimmune disease and not for transplantation. The search for analogues has led to the development of MNA 715 and 279, derivatives of A77 1726. Previous limited experimental experience has shown these MNAs to prevent skin allograft and xenograft rejection and graft-versus-host disease in rodents, and to reverse ongoing allograft rejection. The aim of the present study was to verify the efficacy of these MNAs in a cardiac retransplant model of sensitized rats, concerning prevention of accelerated rejection, inhibition of antibody production and interaction with cyclosporin A (CsA). Heterotopic cardiac transplantation and retransplantation in Dark Agouti (DA) to Piebald Virol Glaxo (PVG) rats was used. Subgroups of rats were given either CsA, MNA 715, MNA 279 or combined CsA/MNA for 10 days starting either day 0 or day -1, as of regrafting or no treatment. Titres of allospecific IgM and IgG were quantitated by flow cytometry. Ten days of MNA 715 or 279 from day -1 prevented accelerated rejection of the retransplant, as did CsA. Neither treatment given from day 0 prevented rejection within 24 h. However, a combination of MNA 715 or 279 and CsA from day 0 effectively prevented accelerated regraft rejection. Production of specific alloantibodies was reduced in all immunosuppressed subgroups, IgG titres at day 7 in MNA-treated subgroups being significantly lower compared with those in the CsA-treated subgroup. In conclusion, MNA 715 and 279 were shown to be potent immunosuppressants with the capacity to prevent accelerated regraft rejection in rat cardiac transplants, most efficiently in combination with CsA, and to suppress specific alloantibody production.

Alkynes↗
PubMed1998

The effects of leflunomide and cyclosporin A on rejection of cardiac allografts in the rat.

Leflunomide is a new low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate-dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. As the mechanisms of action of leflunomide and cyclosporin A (CsA) are different, we postulated a synergistic effect of the two drugs and tested graft survival following leflunomide administration alone or in combination with CsA in a rat cardiac transplantation model. Low- and high-responder rat strain combinations were used in parallel and the experiments were performed both with and without challenge with Linomide, an immunomodulator which promotes graft rejection in this model. In the low-responder rat strain combination (Piebald Virol Glaxo graft to Dark Agouti recipient; PVG to DA), graft survival appeared to be a dichotomous variable, being characterized by tolerance or early rejection. Leflunomide (10 or 5 mg/kg) given for 10 days induced tolerance and CsA did likewise; the addition of Linomide abolished the immunosuppressive effect of leflunomide but not that of CsA. In the high-responder combination (DA to PVG), no tolerance was seen and graft survival was moderately prolonged both after leflunomide and after CsA treatment; the addition of Linomide to CsA or to leflunomide (5 mg/kg) abolished the immunosuppressive effect of the drugs. However, when CsA-Linomide or leflunomide-Linomide were supplemented with the second immunosuppressive drug, leflunomide or CsA respectively, graft survival was significantly prolonged (P < 0.001 in both cases). This suggests leflunomide and CsA have additive potential.

Animals↗
PubMed1998

Malononitrilamides 715 and 279 prolong rat cardiac allograft survival, reverse ongoing rejection, inhibit allospecific antibody production and interact positively with cyclosporin.

A77 1726 is a malononitrilamide (MNA) and the active metabolite of leflunomide, which has been extensively investigated and shown to be a potent immunosuppressive drug. However, the half-life of A77 1726 is about 15-18 days in humans and leflunomide is therefore currently being developed for the treatment of autoimmune disease and not for transplantation. Search for analogues has led to the discovery of MNA 715 and 279, derivatives of A77 1726. Previous experimental experience of these compounds is still limited. The aim of the present study was to verify the efficacy of these MNAs concerning prevention and reversal of rejection, inhibition of antibody production and interaction with cyclosporin A (CsA). Heterotopic cardiac transplantation in DA to PVG rats was used. Subgroups of rats were given either CsA, MNA 715 or MNA 279 for 10 days, starting at either day 0 or day 4, or received no treatment. Titres of allospecific immunoglobulin M (IgM) and immunoglobulin G (IgG) were quantified by flow cytometry. Ten days of induction with MNA 715 or 279 produced significantly longer graft survival than in controls. Treatment from day 4 onwards, when acute rejection was established, rescued all grafts. Allospecific production of IgM or IgG was absent during MNA induction and was suppressed in animals receiving a rescue course of MNA. The transplant model was potentiated by addition of the immunomodulator quinolone-3-carboxamide (Linomide), which eliminates the effect of CsA and other immunosuppressants. The combined treatment with MNA and CsA was successful in overcoming the challenge of Linomide, demonstrating the additive effects of the two drugs. In conclusion, MNA 715 and 279 were shown to be potent immunosuppressants, preventing and reversing acute allograft rejection, inhibiting and suppressing allospecific antibody production, and the drugs interacted positively with CsA.

Alkynes↗
PubMed1998

Accuracy of noninvasive ultrasonic volume measurements on human kidney transplants. Presentation of a new formula.

PURPOSE: To evaluate the precision in volume measurement on human kidney transplants with the aid of noninvasive ultrasonic technique. MATERIAL AND METHODS: A Philips P700 ultrasound machine was used for noninvasive volume determination of 28 porcine kidneys compared to plethysmography. Also, the volume of 46 human transplanted kidneys in situ were measured by ultrasound. Since the configuration of the two types of kidneys differed, a new formula for volume measurement, suitable for kidney transplants, was developed with the aid of clay model experiments. RESULTS: With the standard ellipsoid formula the accuracy of ultrasonic volume determination of the porcine kidneys was good compared with plethysmography, with intra- and interobserver variability of 10.9 and 9.2%, respectively. However, since the width and depth in relation to length of the transplanted kidneys were greater than in the porcine ones (55 vs. 47.5% and 54 vs. 28%, p < 0.01), a new ellipsoid formula was created (r = 1.0, p < 0.0001). CONCLUSION: Noninvasive ultrasonic kidney volume measurements show an acceptable reproducibility (CV 10%). Since the previously used formula for calculating kidney volume was inaccurate on human kidney transplants, a new and accurate ellipsoid formula fitting for human transplanted kidneys is suggested.

Adult↗
PubMed1998

Overexpression of ras is an independent prognostic factor in colorectal adenocarcinoma.

The expression of ras was investigated by using immunohistochemistry in 245 primary colorectal adenocarcinomas and 49 corresponding metastases in the lymph nodes. One hundred and forty-four (59%) of the primary tumours presented as ras positive and 37 (76%) were positive in metastases. The ras expression was positively related to cell proliferation (p=0.01) and significantly increased in tumours with aneuploidy (68%) compared to tumours with diploidy (51%) and tetraploidy (53%, p=0.01). The frequency of ras expression was increased from Dukes' stage A to stages B-D (41% vs 62%, p=0.01). ras expression was compared in 40 paired primary tumours and their corresponding metastases, and the difference in expression did not reach statistical significance (73% vs 83%, p=0.32). In survival analyses, ras overexpression predicted a poor prognosis independent of Dukes' stage, DNA ploidy and S-phase fraction (p=0.049). We did not find any significant relationship between ras expression and patients' sex, age, tumour location, growth pattern, differentiation, p53 expression or heat shock protein. The results indicate that the alteration of ras expression may be involved in the instability of DNA and cellular overproliferation, but not in the progression to advanced stage and the development of metastases. The expression of ras was an important biological marker for evaluating the prognosis in patients with colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Long-term duct-occluded segmental pancreatic autografts: absence of microvascular diabetic complications.

BACKGROUND: Current insulin therapies for control of glucose metabolism in patients with type I diabetes mellitus prevent major metabolic consequences of insulin deficiency, but none prevents or arrests long-term complications. In experimental models of canine diabetes, retinopathy, neuropathy, and nephropathy have been shown to develop within 5 years. The aim of this study was to determine in a canine model whether glucose control provided by segmental duct-occluded pancreas autografts could prevent the long-term complications of diabetes. METHODS: Thirty-five outbred mongrel dogs underwent segmental pancreas autotransplantation with residual pancreatectomy. Follow-up over 5 years included endocrine, retinal fundus photography, fluorescein angiography, and nerve conduction studies. At endpoint, analysis of organ specific changes was undertaken. RESULTS: Long-term survival was achieved in 14 dogs for 4 to 5 years and in 3 dogs for 3 to 5 years. Glycosylated hemoglobin levels remained within normal limits, although response to glucose challenge was suboptimal. Fundus photography and fluorescein angiography demonstrated the absence of retinal vascular aneurisms, capillary leakage, and obliteration. Retinal digest showed no vascular changes and normal endothelial/pericyte ratios. Nerve conduction was normal, and histology of nerves revealed normal density of myelinated fibers and absence of intrafascicular vessels and glycogen deposits, with no change in spectrum of fiber diameters and ovoids. Renal histology revealed no evidence of nephropathy with normal glomerular basement membranes. CONCLUSIONS: We have demonstrated that duct-occluded segmental pancreatic autografts are capable of providing satisfactory metabolic control for up to 5 years, thereby preventing development of the long-term microvascular complications of diabetes.

Animals↗
PubMed1997

Activation of alloreactive natural killer cells is resistant to cyclosporine.

BACKGROUND: We have previously shown that cytotoxic T lymphocytes (CTL) with alloreactivity were induced when Wistar Furth (WF; RT1u) rats were immunized with allogeneic Brown Norway (BN; RT1n) cells. In contrast, when BN rats were immunized with WF cells, the allospecific response was confined to alloreactive natural killer (NK) cells, and no CTL activity was observed. In this study, the effect of cyclosporine (CsA) on the activation of alloreactive NK cells in vivo was analyzed. METHODS: Distinct peritoneal effector cells from rats immunized with allogenic cells with or without concomitant CsA and/or interleukin (IL) 2 treatment were tested for specific cytolytic activity. Furthermore, the presumptive role of NK cells in rejection immunity was addressed in a cardiac graft model. RESULTS: The results showed that doses of CsA that completely inhibited the activation of alloreactive CTL, only marginally affected the activation of alloreactive NK cells. We also showed that CsA treatment failed to prolong graft survival in BN recipients of WF hearts. Treatment of BN rats with CsA/IL-2 during immunization with allogeneic WF cells resulted in concomitant induction of alloreactive NK cells and alloreactive CTL. CONCLUSIONS: We have demonstrated that CsA failed to suppress the activation of alloreactive NK cells. Consequently, the cardiac graft survival in the donor-recipient combination known to activate alloreactive NK cells was not significantly prolonged by CsA treatment, emphasizing the involvement of NK cells as effectors in organ rejection. Furthermore, the parallel emergence of alloreactive NK cells and CTL only in the presence of CsA/IL-2 indicated that CsA interfered with alloreactive NK cell-associated suppression of CTL activated by allogeneic tissue.

Animals↗
PubMed1997

Simultaneous pancreas and kidney transplant rejection: separate or synchronous events?

The results of simultaneous pancreas and kidney transplantation (SPK) cannot be matched by pancreas transplantation alone (PTA), in part because an independent diagnosis of pancreas graft rejection remains difficult. The relationship between rejection of the pancreas and rejection of the kidney is poorly understood, and it is not known whether simultaneous transplantation of both organs confers true protection to either graft. To study these questions, reliable canine allotransplant models of kidney transplantation alone (KTA), PTA, and SPK were established. Sixty-seven mongrel dogs received KTA (n=21), PTA (n=23), or SPK (n=23) with either no immunosuppression, low-dose cyclosporine (CsA)-based immunosuppression, or high-dose CsA-based immunosuppression. Needle core biopsy (NCB) and fine needle aspiration biopsy (FNAB) were performed at 0, 2, 4, 7, 9, 11, 14, 21, and 30 days or at the time of graft failure. Pancreas and kidney graft survival after SPK was significantly shorter in dogs given low-dose CsA than in dogs given high-dose CsA (pancreas, P<0.04; kidney, P<0.03). Concurrent NCBs and FNABs were performed on 227 occasions in pancreas grafts and 229 occasions in kidney grafts. The time to initial evidence of rejection by NCB was not different in any immunosuppressed group. Synchronous rejection occurred in 73% of immunosuppressed SPK biopsies. Kidney-only rejection occurred in 23% of biopsies and pancreas-only rejection occurred in only 3% after SPK. All markers of pancreas graft rejection were poor, with the most sensitive being NCB of the simultaneously transplanted kidney. In summary, recipients of SPK required more immunosuppression than recipients of PTA, and improved PTA survival should be achievable with more sensitive markers of rejection. Markers of kidney rejection were the most sensitive indicators of pancreas rejection, and independent pancreas rejection was uncommon after SPK.

Animals↗
PubMed1997

Allogeneic heart transplantation activates alloreactive NK cells.

The ability of natural killer (NK) cells to recognize and reject transplants has so far been shown in hematopoietic grafts only. This study was designed to ascertain whether NK cells may also be involved in the rejection of transplanted organs. In most rat strain combinations, immunization with allogeneic cells induces a T cell response with cytotoxic T lymphocyte (CTL) activation. We have previously found one exception to this. In contrast to Wistar Furth rats (WF, RT1u), which manifest allospecific CTL activation in response to immunization with Brown Norway (BN, RT1n) cells, BN rats immunized with repeated intraperitoneal (i.p.) injections of allogeneic WF spleen cells manifest activation of alloreactive NK effector cells. The alloreactive NK cells were of the TCR-, CD3-, CD8+, and NKR-P1 intermediate phenotype and killed target cells with alloselectivity. In this study we used a heart transplantation model to study the rejection response of BN rats receiving WF grafts. NK cell infiltration was greater in WF hearts transplanted to BN recipients than in BN hearts transplanted to WF recipients. Furthermore, the extent of T cell infiltration was less in BN recipients. In WF rats transplanted with allogeneic BN hearts, CTL were activated in response to i.p. challenge with allogeneic BN cells, whereas BN rats transplanted with allogeneic WF hearts and i.p. challenged with allogeneic WF cells, manifested activation of alloreactive NK cells but no measurable activation of classic CTL. The alloreactive NK cells killed their allogeneic targets with specificity and with potency comparable to that of CTL. Furthermore, WF grafts were rejected in BN recipients as efficiently as were BN grafts in WF recipients. These results not only show cardiac allografts to be able to activate alloreactive NK cells, but also suggest that NK cells may be involved in the rejection of solid organ transplants and function as classic CTL in certain donor-recipient combinations.

Animals↗