Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation.

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002-2003 and 2011-2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney-only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p < 0.0001), listed patients at our center waited less time for transplantation (645 vs. 1045 days; p < 0.0001), and our center had higher transplantation rates and lower numbers of waiting list deaths. This was most apparent for older patients (aged >65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death-censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients.

Donors With Immune Thrombocytopenia: Do They Pose a Risk to Transplant Recipients?

Transplant-mediated alloimmune thrombocytopenia (TMAT) from donors with immune thrombocytopenia (ITP) can result in significant bleeding complications in the recipient. The risk to a recipient of TMAT if they receive an organ from a donor with ITP is unknown. The outcomes of recipients of organs from deceased donors with ITP recorded in the UK Transplant Registry between 2000 and 2015 were reviewed. Twenty-one deceased organ donors had a predonation diagnosis of ITP. These donors were significantly more likely to have died from intracranial hemorrhage than were all other deceased organ donors (85% vs. 57%, p < 0.001). Organs from donors with ITP resulted in 49 organ transplants (31 kidney, 14 liver, four heart), with only one case of TMAT, which occurred in a liver transplant recipient and resulted in death from bleeding complications 18 days posttransplantation. The recipient of a kidney from the same organ donor was not affected. Unadjusted 5-year patient and graft survival was significantly worse for liver transplant recipients from donors with ITP compared with liver transplant recipients from donors without ITP (64% vs. 85%, p = 0.012). Organs from donors with ITP may be considered for transplantation, but livers should be used with caution.

Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor-Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching.

We have assessed whether HLA immunogenicity as defined by differences in donor-recipient HLA amino-acid sequence (amino-acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitization to HLA, and also prediction of the risk of an individual donor-recipient HLA mismatch to induce donor-specific antibody (DSA). HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of AMS, EpMS, and EMS on the development of allosensitization (calculated reaction frequency [cRF]) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that AMS (odds ratio [OR]: 1.44 per 10 units, 95% CI: 1.02-2.10, p = 0.04) and EMS (OR: 1.27 per 10 units, 95% CI: 1.02-1.62, p = 0.04) were independently associated with the risk of developing sensitization to HLA (cRF > 15%). AMS, EpMS, and EMS were independently associated with the development of HLA-DR and HLA-DQ DSA, but only EMS correlated with the risk of HLA-A and -B DSA development. Differences in donor-recipient HLA amino-acid sequence and physicochemical properties enable better assessment of the risk of HLA-specific sensitization than conventional HLA matching.

Transfer of HLA-Specific Allosensitization From a Highly Sensitized Deceased Organ Donor to the Recipients of Each Kidney.

We report for the first time the adoptive transfer of donor HLA-specific allosensitization in two recipients following kidney transplantation from a highly sensitized donor. Kidneys from a donation after circulatory death donor were transplanted into two nontransfused, HLA-specific antibody negative males receiving their first transplant. Antibody screening 7 days after transplant showed high level de novo IgG HLA class I- and class II-specific antibodies in both recipients, with largely overlapping antibody profiles but no antibodies to donor HLA. The unusually rapid appearance of de novo alloantibodies in immunosuppressed nonsensitized recipients and absence of donor HLA-specific antibody prompted testing of stored donor serum that revealed high antibody levels with specificities very similar to those seen in both recipients, but in addition the presence of strong antibodies to each recipient HLA. Alloantibody levels gradually declined but were still detectable at 3 months. These findings suggest that alloreactive passenger B cells/plasma cells within the kidneys of highly sensitized donors may give rise to rapid development of posttransplant de novo HLA-specific alloantibodies. While the clinical significance of this phenomenon is uncertain it provides one explanation for the appearance of de novo HLA-specific antibodies directed against third party but not donor HLA.

Early graft loss after kidney transplantation: risk factors and consequences.

Early graft loss (EGL) after kidney transplantation is a catastrophic outcome that is assumed to be more likely after the use of kidneys from suboptimal donors. We therefore examined its incidence, risk factors and consequences in our center in relation to different donor types. Of 801 recipients who received a kidney-only transplant from deceased donors, 50 (6.2%) suffered EGL within 30 days of transplantation. Significant risks factors for EGL were donation after circulatory death (DCD) (odds ratio [OR] 2.88; p = 0.006), expanded criteria donor (ECD) transplantation (OR 4.22; p = 0.010), donor age (OR 1.03; p = 0.044) and recipient past history of thrombosis (OR 4.91; p = 0.001). Recipients with EGL had 12.28 times increased risk of death within the first year, but long-term survival was worse for patients remaining on the waiting list. In comparison with patients on the waiting list but not transplanted, and with all patients on the waiting list, the risk of death after EGL decreased to baseline 4 and 23 months after transplantation, respectively. Our findings suggest that DCD and ECD transplantation are significant risk factors for EGL, which is a major risk factor for recipient death. However, long-term mortality is even greater for those remaining on the waiting list.

Use of Ex Vivo Normothermic Perfusion for Quality Assessment of Discarded Human Donor Pancreases.

A significant number of pancreases procured for transplantation are deemed unsuitable due to concerns about graft quality and the associated risk of complications. However, this decision is subjective and some declined grafts may be suitable for transplantation. Ex vivo normothermic perfusion (EVNP) prior to transplantation may allow a more objective assessment of graft quality and reduce discard rates. We report ex vivo normothermic perfusion of human pancreases procured but declined for transplantation, with ABO-compatible warm oxygenated packed red blood cells for 1-2 h. Five declined human pancreases were assessed using this technique after a median cold ischemia time of 13 h 19 min. One pancreas, with cold ischemia over 30 h, did not appear viable and was excluded. In the remaining pancreases, blood flow and pH were maintained throughout perfusion. Insulin secretion was observed in all four pancreases, but was lowest in an older donation after cardiac death pancreas. Amylase levels were highest in a gland with significant fat infiltration. This is the first study to assess the perfusion, injury, as measured by amylase, and exocrine function of human pancreases using EVNP and demonstrates the feasibility of the approach, although further refinements are required.

Baseline donor chronic renal injury confers the same transplant survival disadvantage for DCD and DBD kidneys.

Histological assessment of baseline chronic kidney injury may discriminate kidneys that are suitable for transplantation, but has not been validated for appraisal of donation after circulatory death (DCD) kidneys. 'Time-zero' biopsies for 371 consecutive, solitary, deceased-donor kidneys transplanted at our center between 2006 and 2010 (65.5% DCD, 34.5% donation after brain death [DBD]) were reviewed and baseline chronic degenerative injury scored using Remuzzi's classification. High scores correlated with donor age and extended criteria donors (42% of donors), but the spectrum of scores was similar for DCD and DBD kidneys. Transplant outcomes for kidneys scoring from 0 to 4 were comparable (1 and 3 year graft survival 95% and 92%), but were much poorer for kidneys scoring ≥5, with 1 year graft survival only 73%, and 12.5% suffering primary nonfunction. Critically, high Remuzzi scores conferred the same survival disadvantage for DCD and DBD kidneys. On multi-variable regression analysis, time-zero biopsy score was the only independent predictor for graft survival, whereas one-year graft estimated glomerular filtration rate (eGFR) correlated with donor age and biopsy score. In conclusion, the relationship between severity of chronic kidney injury and transplant outcome is similar for DCD and DBD kidneys. Kidneys with Remuzzi scores of ≤4 can be implanted singly with acceptable results.

Successful transplantation of kidneys from elderly circulatory death donors by using microscopic and macroscopic characteristics to guide single or dual implantation.

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual-implanted kidney; its pair continued to function satisfactorily. Death-censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual-implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased-donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.

When one becomes more: minimum renal artery length in laparoscopic live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy may convert short main arteries into multiple arteries, increasing the technical challenge of implantation. We evaluated our experience to identify factors predictive of multiple arteries after laparoscopic nephrectomy. METHODS: All laparoscopic nephrectomies from the start of our program in November 2002 until June 2013 were studied, and preoperative imaging reviewed for donor artery length and multiplicity together with operative findings. RESULTS: A total of 287 consecutive laparoscopic live donor nephrectomies (64 right and 223 left nephrectomies) were studied. Renal artery length was measured from preoperative donor magnetic resonance or computed tomography angiogram and nephrectomy performed using a laparoscopic stapling device. Nine left kidneys with a single artery (6, 7, 9, 10, 11, 12, 13, 14, and 16 mm in length) and five right kidneys with a single artery (5, 13, 15, 20, and 26 mm) on imaging resulted in multiple renal arteries at implantation. Complex renal vein anatomy was associated with multiple arteries following retrieval. CONCLUSION: A main renal artery length of more than 16 mm on the left and 26 mm on the right is unlikely to result in multiple arteries to implant. The possibility of multiple arteries should be borne in mind when the donor renal artery is short.

Postoperative CT in pancreas transplantation.

AIM: To examine the usage and value of computed tomography (CT) following simultaneous pancreas and kidney (SPK) transplantation. MATERIALS AND METHODS: Indications for postoperative CT, key findings, and their influence on management were determined by retrospective analysis. RESULTS: Ninety-eight patients underwent 313 CT examinations. Common indications for the examinations included suspected intra-abdominal collection (31.1%) and elevated serum amylase/lipase (24.1%). CT findings most frequently showed non-specific mild inflammation (27.6%), a normal scan (17.1%) and fluid collections (16.3%). High capillary blood glucose (CBG) was associated with resultant CT demonstration of graft vascular abnormalities, but otherwise, particular clinical indications were not associated with specific CT findings. CONCLUSION: Clinical findings in patients with SPK transplants are non-specific. The pattern of abnormalities encountered is significantly different to those seen in native pancreatic disease and demands a tailored protocol. CT enables accurate depiction of vascular abnormalities and fluid collections, thus reducing the number of surgical interventions that might otherwise be required. Elevated CBG should prompt urgent CT to exclude potentially reversible vascular complications.

Standardized deceased donor kidney donation rates in the UK reveal marked regional variation and highlight the potential for increasing kidney donation: a prospective cohort study†.

BACKGROUND: The UK has implemented a national strategy for organ donation that includes a centrally coordinated network of specialist nurses in organ donation embedded in all intensive care units and a national organ retrieval service for deceased organ donors. We aimed to determine whether despite the national approach to donation there is significant regional variation in deceased donor kidney donation rates. METHODS: The UK prospective audit of deaths in critical care was analysed for a cohort of patients who died in critical care between April 2010 and December 2011. Multivariate logistic regression was used to identify the factors associated with kidney donation. The logistic regression model was then used to produce risk-adjusted funnel plots describing the regional variation in donation rates. RESULTS: Of the 27 482 patients who died in a critical care setting, 1528 (5.5%) became kidney donors. Factors found to influence donation rates significantly were: type of critical care [e.g. neurointensive vs general intensive care: OR 1.53, 95% confidence interval (CI) 1.34-1.75, P<0.0001], patient ethnicity (e.g. 'Asian' vs 'white': OR 0.17, 95% CI 0.11-0.26, P<0.0001), age (e.g. age >69 vs age 18-39 yr: OR 0.2, 0.15-0.25, P<0.0001), and cause of death [e.g. 'other' (excluding 'stroke' and 'trauma') vs 'trauma': OR 0.04, 95% CI 0.03-0.05, P<0.0001]. Despite correction for these variables, kidney donation rates for the 20 UK kidney donor regions showed marked variation. The overall standardized donation rate ranged from 3.2 to 7.5%. Four regions had donation rates of >2 standard deviations (sd) from the mean (two below and two above). Regional variation was most marked for donation after circulatory death (DCD) kidney donors with 9 of the 20 regions demonstrating donation rates of >2 sd from the mean (5 below and 4 above). CONCLUSIONS: The marked regional variation in kidney donation rates observed in this cohort after adjustment for factors strongly associated with donation rates suggests that there is considerable scope for further increasing kidney donation rates in the UK, particularly DCD.

Structural and electrostatic analysis of HLA B-cell epitopes: inference on immunogenicity and prediction of humoral alloresponses.

PURPOSE OF REVIEW: The immunogenic capacity of donor human leukocyte antigen (HLA) to induce humoral immune responses is not an intrinsic property of the mismatched alloantigen but depends on the HLA phenotype of the recipient. In recent years, advances in molecular sequence technology and information from X-ray crystallography have enabled structural comparison of donor and recipient HLA type providing an opportunity for a more rational approach for determining HLA compatibility. In this article, we review studies investigating the molecular basis of antibody-antigen interactions and present computational approaches to determine the complex physiochemical and structural properties of B-cell epitopes. RECENT FINDINGS: The relative immunogenicity of individual HLA mismatches may be predicted from analysis of polymorphic amino acids at continuous and discontinuous HLA sequence positions. The use of alloantigen sequence information alone, however, provides limited insight into key determinants of B-cell epitope immunogenicity, such as the orientation, accessibility and physiochemical properties of amino acid side chains. Advances in computational molecular modelling techniques now enable assessment of HLA-alloantibody interactions at the atomic level. Recent evidence supports a strong link between HLA B-cell epitope surface electrostatic potential and their immunogenicity. SUMMARY: Assessment of the surface electrostatic properties of HLA alloantigens and computational analyses of HLA-alloantibody interactions represent a promising area for future research into the molecular basis of HLA immunogenicity and antigenicity.

Time to death after withdrawal of treatment in donation after circulatory death (DCD) donors.

PURPOSE: Controlled donation after circulatory death (DCD) donors make an important contribution to organ transplantation but there is considerable scope for further increasing the conversion of potential to actual DCD organ donors. The period between withdrawal of life-supporting treatment and death (the withdrawal period) is a major determinant of whether organ donation proceeds and it is therefore timely to review recent relevant studies in this area. RECENT FINDINGS: The duration and haemodynamic nature of the withdrawal period is extremely variable, and clinical guidelines for management of the potential donor during this period differ widely. Recent evidence suggests that kidneys from DCD donors with a prolonged withdrawal period can be used to increase the number of transplants performed and provide satisfactory graft function, suggesting that it is not the duration but the haemodynamic profile of the donor during this phase that are important. This suggestion questions the relevance of clinical indices predicting death within 1 h of treatment withdrawal. SUMMARY: Future studies should aim to define clinical and physiological variables during the withdrawal period that can be used to maximize well tolerated use of organs from potential DCD donors; these thresholds are likely to differ according to organ type.

A miniature X-ray emission spectrometer (miniXES) for high-pressure studies in a diamond anvil cell.

Core-shell X-ray emission spectroscopy (XES) is a valuable complement to X-ray absorption spectroscopy (XAS) techniques. However, XES in the hard X-ray regime is much less frequently employed than XAS, often as a consequence of the relative scarcity of XES instrumentation having energy resolutions comparable with the relevant core-hole lifetimes. To address this, a family of inexpensive and easily operated short-working-distance X-ray emission spectrometers has been developed. The use of computer-aided design and rapid prototype machining of plastics allows customization for various emission lines having energies from ∼3 keV to ∼10 keV. The specific instrument described here, based on a coarsely diced approximant of the Johansson optic, is intended to study volume collapse in Pr metal and compounds by observing the pressure dependence of the Pr Lα emission spectrum. The collection solid angle is ∼50 msr, roughly equivalent to that of six traditional spherically bent crystal analyzers. The miniature X-ray emission spectrometer (miniXES) methodology will help encourage the adoption and broad application of high-resolution XES capabilities at hard X-ray synchrotron facilities.

Outcomes of simultaneous pancreas-kidney transplantation from brain-dead and controlled circulatory death donors.

BACKGROUND: Organ scarcity has prompted increased use of organs from donation after circulatory death (DCD) donors. An early single-centre experience of simultaneous pancreas-kidney (SPK) transplantation from controlled DCD donors is described here. METHODS: Outcomes of SPK transplants from DCD and donation after brain death (DBD) donors between August 2008 and January 2011 were reviewed retrospectively. RESULTS: SPK transplants from 20 DCD and 40 DBD donors were carried out. Donor and recipient characteristics were similar for both groups, although pancreas cold ischaemia times were shorter in DCD recipients: median (range) 8·2 (5·9-10·5) versus 9·5 (3·8-12·5) h respectively (P = 0·004). Median time from treatment withdrawal to cold perfusion was 24 (range 16-110) min for DCD donors. There were no episodes of delayed pancreatic graft function in either group; the graft thrombosis rates were both 5 per cent. Similarly, there were no differences in haemoglobin A1c level at 12 months: median (range) 5·4 (4·9-7·7) per cent in DCD group versus 5·4 (4·1-6·2) per cent in DBD group (P = 0·910). Pancreas graft survival rates were not significantly different, with Kaplan-Meier 1-year survival estimates of 84 and 95 per cent respectively (P = 0·181). CONCLUSION: DCD SPK grafts had comparable short-term outcomes to DBD grafts, even when procured from selected donors with a prolonged agonal phase.

Ultrafast transitions from solid to liquid and plasma states of graphite induced by x-ray free-electron laser pulses.

We used photon pulses from an x-ray free-electron laser to study ultrafast x-ray-induced transitions of graphite from solid to liquid and plasma states. This was accomplished by isochoric heating of graphite samples and simultaneous probing via Bragg and diffuse scattering at high time resolution. We observe that disintegration of the crystal lattice and ion heating of up to 5 eV occur within tens of femtoseconds. The threshold fluence for Bragg-peak degradation is smaller and the ion-heating rate is faster than current x-ray-matter interaction models predict.

Antibody-mediated rejection--an ounce of prevention is worth a pound of cure.

The presence of preformed, donor-specific alloantibodies inpatients undergoing renal transplantation is associated with a high risk of hyperacute and acute antibody-mediated rejection (ABMR), and often limits potential recipients' access to organs from living and deceased donors. Over the last decade, understanding of ABMR has improved markedly and given rise to numerous, diverse strategies for the transplantation of allosensitized recipients. Antibody desensitization programs have been developed to allow renal transplant recipients with a willing but antibody-incompatible living donor to undergo successful transplantation, whereas kidney paired exchange schemes circumvent the antibody incompatibility altogether by finding suitable pairs to donors and recipients. Recognizing the complexity of ABMR and the recent developments that have occurred in this important clinical research field, the Roche Organ Transplantation Research Foundation (ROTRF) organized a symposium during the XXIII Congress of The Transplantation Society in Vancouver, Canada, to discuss current understanding in ABMR and ways to prevent it. This Meeting Report summarizes the presentations of the symposium, which addressed key areas that included the interactions between alloantibodies and the complement system in mediating graft injury, technological advancements for assessing antibody-mediated immune responses to HLA antigens, and the potential benefits and challenges of desensitization and kidney paired donation schemes.

Expansion of the kidney donor pool by using cardiac death donors with prolonged time to cardiorespiratory arrest.

Donation after Cardiac Death (DCD) is an increasingly important source of kidney transplants, but because of concerns of ischemic injury during the agonal phase, many centers abandon donation if cardiorespiratory arrest has not occurred within 1 h of controlled withdrawal of life-supporting treatment (WLST). We report the impact on donor numbers and transplant function using instead a minimum 'cut-off' time of 4 h. The agonal phase of 173 potential DCD donors was characterized according to the presence or absence of: acidemia; lactic acidosis; prolonged (>30 min) hypotension, hypoxia or oliguria, and the impact of these characteristics on 3- and 12-month transplant outcome evaluated by multivariable regression analysis. Of the 117 referrals who became donors, 27 (23.1%) arrested more than 1 h after WLST. Longer agonal-phase times were associated with greater donor instability, but surprisingly neither agonal-phase instability nor its duration influenced transplant outcome. In contrast, 3- and 12-month eGFR in the 190 transplanted kidneys was influenced independently by donor age, and 3-month eGFR by cold ischemic time. DCD kidney numbers are increased by 30%, without compromising transplant outcome, by lengthening the minimum waiting time after WLST from 1 to 4 h.

T cell requirements for the rejection of renal allografts bearing an isolated class I MHC disparity.

This study has examined the cellular and humoral responses underlying the rejection of rat renal allografts bearing an isolated RT1Aa class I MHC disparity. RT1Aa disparate kidneys were rejected promptly by high responder RT1u but not by low responder RT1c recipients (median survival time 10 d and greater than 100 d, respectively). The magnitude and phenotype of the cellular infiltrate were similar in rejecting and nonrejecting RT1Aa disparate kidneys. Paradoxically, graft infiltrating cells and spleen cells from RT1u recipients showed minimal ability to lyse donor strain lymphoblasts in vitro, whereas effector cells from RT1c recipients showed modest levels of cytotoxicity. Injection of RT1u rats with MRC OX8 mAb was highly effective at selectively depleting CD8+ cells from graft recipients but had no effect in prolonging the survival of RT1Aa disparate grafts despite the complete absence of CD8+ cells from the graft infiltrate, which included numerous CD4+ T cells and macrophages. RT1u, but not RT1c, recipients mounted a strong alloantibody response against RT1Aa disparate kidneys. Immune serum obtained from RT1u recipients that had rejected a RT1Aa disparate graft was able, when injected into cyclosporin-treated RT1u recipients, to restore their ability to reject a RT1Aa, but not a third-party RT1c, kidney. These results suggest that CD8+ cells in general and CD8+ cytotoxic effector cells in particular are unnecessary for the rapid rejection of RT1Aa class I disparate kidney grafts by high responder RT1u recipients. By implication, CD4+ T cells alone are sufficient to cause prompt rejection of such grafts and they may do so by providing T cell help for the generation of alloantibody.

Prolonged survival of actively enhanced rat renal allografts despite accelerated cellular infiltration and rapid induction of both class I and class II MHC antigens.

Administration of 1 ml of donor whole blood 7 d before renal transplantation produces long-term (greater than 100 d) graft survival in the DA (RT1a) into PVG (RT1c) rat strain combination. Using this model, the pattern and phenotype of infiltrating leukocytes were examined in rejecting and enhanced renal allografts, at days 1, 3, 5, and 7 after transplantation, by immunohistologic techniques. Paradoxically, enhanced grafts showed a more rapid and substantial leukocyte infiltrate, the phenotype of which was similar to that in rejecting grafts except for a reduced number of MRC OX-8+ cells and MRC OX-39+ cells. Graft infiltrating cells and splenocytes from transfused animals showed similar, although modest, levels of both nonspecific cytotoxicity and alloantigen-specific cytotoxicity. Immunohistologic analysis of MHC antigen distribution within the allograft revealed, unexpectedly, that enhanced grafts underwent an accelerated and extensive induction of both donor class I and class II MHC antigens. These findings were confirmed by allospecific quantitative absorption analysis, which showed severalfold increases in class I and class II MHC antigens by day 3 in enhanced grafts but not until day 5 in rejecting grafts. An additional observation was the more rapid disappearance of donor interstitial cells from enhanced grafts. These findings emphasize the overwhelming suppressive effect induced by an organ allograft after preoperative blood transfusion despite the associated induction of large numbers of potential effector cells and increased target antigen density within the graft.