Natural killer cell activity following thermal injury

The role of natural killer cell activity in immunosurveillance following thermal injury remains unknown. We utilize a chromium-51-release assay of K562 targets to monitor NK activity. NK activity of peripheral blood mononuclear cells of severely burned patients (BSA greater than 20%) was determined once a week until the convalescence period was completed. From the second week after thermal injury, impairment of NK activity was demonstrated, but the differences did not reach statistical significance. However, a correlation was found between decline of NK activity and incidences of septic complications. Surprisingly, no decline in NK activity was observed in the first week after thermal injury.     

个体化免疫耐受的诱导与调节性T细胞

免疫耐受的诱导是器官移植免疫领域的重要组成部分和最高追求目标,它基于对移植抗原识别、提呈以及免疫系统的激活和应答等免疫学本质的认识。但是,在成功诱导免疫耐受之前,如何对器官移植受者实施个体化免疫耐受诱导,从而使免疫抑制剂和个体化治疗措施实现最优化的搭配,来达到预防和治疗排斥反应的效果最佳、不良反应最小的理想状态,仍然是移植工作者不断探索和仍未解决的难题。本文综合国际核心期刊报道内容,从免疫耐受诱导机制、可操作性免疫耐受的实现、个体化免疫耐受诱导新策略及调节性T细胞在个体化免疫耐受中的应用,并结合本中心调节性T细胞临床和基础研究成果综合讨论个体化免疫耐受诱导策略和未来展望。     

Exercise tolerance changes following renal transplantation

Maximal exercise capacity was measured in 20 nondiabetic patients with end-stage renal disease before and soon after successful renal transplantation. Maximal oxygen consumption increased significantly in all patients posttransplant. Increases in maximal heart rate and heart rates at 70% of maximal levels were also observed. The changes in maximal oxygen consumption were not significantly correlated with changes in hematocrit. The removal of uremia may result in improved functioning of one or more of the systems involved in oxygen transport and utilization that determine exercise capacity.     

Association of natural killer cell depletion with induction of mixed chimerism and allograft tolerance in non-human primates

BACKGROUND: Nonmyeloablative T cell depletion followed by donor bone marrow infusion has proved to be an effective approach to induction of mixed chimerism and tolerance of organ allografts in non-human primates. To help define the mechanisms involved we have compared T cell depletion with ATG versus anti-CD2 monoclonal antibody with respect to establishment of mixed chimerism and induction of tolerance. METHOD: Both nonmyeloablative regimens included low dose total body irradiation (1.5 Gy x 2), thymic irradiation (7 Gy), splenectomy and kidney plus donor bone marrow transplantation, followed by a 4-week posttransplant course of cyclosporine. In addition, the ATG group (13 recipients) received antithymocyte globulin, although the LOCD2b group (10 recipients) were treated with an anti-CD2 monoclonal antibody (LOCD2b). RESULTS: In the ATG group, 11 of 13 monkeys developed multilineage chimerism and 9 survived for more than 100 days without kidney allograft rejection. In contrast, 0/10 monkeys in the LOCD2b group developed chimerism, 5 died of infection and 5 suffered progressive rejection; only 1 recipient survived beyond 100 days. Sequential monitoring of peripheral blood mononuclear cells revealed greater T cell (CD3+) depletion in the LOCD2b-treated animals compared to those receiving ATG. However, NK cells (CD16+CD8+) were significantly more depleted in the ATG group and NK function remained abrogated longer after ATG than LOCD2b treatment (3 weeks vs. <5 days). CONCLUSION: Despite excellent T cell depletion by LoCD2b, ATG was more effective in inducing chimerism and tolerance. This difference correlated with anti-NK activity of the two reagents. These data suggest that NK cells may also resist engraftment of allogeneic bone marrow cells in this model.     

Natural killer cells in patients with renal cell cancer

Cytotoxic activity of natural killer (NK) cells in peripheral blood was studied in 60 patients with renal cell carcinoma (RCC) by means of a 51Cr release assay against K 562 cells, homologous and autologous RCC. All patients were tested prior to surgery and thereafter followed up for 1 year. Immunostimulating agents as interferon, levamisole, OMPI, and various bacterial extracts were tested for their boosting capacity on NK cells. Patients with localized tumor showed increased activity in comparison to age-matched controls, whereas NK cell activity and interferon-boosted activity in patients with advanced disease and tumor spread was decreased. Augmentation of NK activity could only be achieved by interferon, while application of levamisole, OMPI, and bacterial extracts resulted rather in suppression of cytotoxic activity.     

Natural killer cell activity in patients with urologic cancer

Cell-mediated cytotoxicity in patients with urologic cancer was studied using the K562 cell line as target cell by a 4-hour chromium-51 release assay. Lysis of target cells by mononuclear cells of a healthy subject, over an 8-hour incubation period, demonstrated a linear function of incubation time and effector:target ratio. Natural killer (NK) cell activity was found decreased (mean 30.6%) in peripheral blood lymphocytes from 42 untreated patients with urologic cancer when compared to 20 healthy subjects (63.6%) and to 10 patients with varicocele, stone disease and benign prostatic hypertrophy (58.1%; p less than 0.05). There was no correlation between NK cell activity and the grade or stage status in bladder cancer patients. No age-dependent changes in NK cell activity could be found between young and aged groups of healthy subjects. Healthy male subjects have higher levels of NK cell activity (77.7%) than healthy female subjects (49.5%). Postoperative NK activity rose in 5 out of 6 cancer patients. It indicates that tumors may have an inhibitory effect on the surveillance activity of NK cells.     

Natural killer cell activation primes macrophages to clear bacterial infection

Natural killer (NK) cells are major cytokine producers during bacterial sepsis, but their precise role is undefined. This study investigates the effect of NK cell depletion with and without prior activation on macrophage function and bacterial clearance during cecal ligation and puncture. Two different NK cell-depleting antibodies were used: anti-asialo-GM1 (GM1), a nonactivating antibody, and anti-NK1.1 (NK1.1), an NK cell-activating antibody. C57BL/6 mice were NK depleted with either GM1 or NK1.1 by intraperitoneal injection 7 and 3 days before experimentation. Control animals received isotype immunoglobulin G. Depletion was confirmed by flow cytometry. Bacterial levels in peritoneal washout, blood, and liver were determined 4 hours after cecal ligation and puncture. Macrophage activation was measured by phagocytosis ability and by production of nitric oxide and interleukin-6. Depletion with GM1 resulted in significantly higher bacterial levels at 4 hours, whereas depletion with NK1.1 had the opposite effect of significantly decreasing bacterial levels. Macrophage phagocytosis ability was significantly increased in mice depleted with NK1.1 compared with those mice depleted with GM1. We conclude that activation of NK cells improves bacterial clearance by priming macrophages to help clear a subsequent bacterial challenge. Macrophages are less able to clear bacteria when NK cells are depleted without activation. NK cells are therefore important in bacterial clearance through interactions with macrophages.     

Natural killer cell activity in patients undergoing minor gynaecological surgery

Natural killer (NK) cell activity was investigated in 24 patients who were undergoing minor gynaecological surgery performed during neurolept, halothane or spinal anaesthesia. The endocrine response to anaesthesia and surgery was monitored using serum cortisol and plasma catecholamine estimations. The surgical trauma was insufficient to elicit an endocrine stress response. No changes in NK cell cytotoxicity occurred in any group during premedication, anaesthesia or surgery. Post-operatively the NK cell activity fell transiently in the two groups that received general anaesthesia (P less than 0.05), whereas no reduction was found in the group that was given spinal anaesthesia. The results indicate that minor surgery induces only small variations in NK cell cytotoxicity and no conclusions can be made, therefore, concerning the influence of different anaesthetic techniques on NK cell cytotoxicity.     

Natural killer cell stimulatory factor (NKSF) augments natural killer cell and antibody-dependent tumoricidal response against colon carcinoma cell lines.

The therapy of colorectal cancer may be improved by biologic response modifiers that enhance natural killer (NK) cell and antibody-dependent tumoricidal mechanisms. This study examined the effect of a recently discovered cytokine purified from the supernatant of an Ebstein-Barr virus-transformed B-lymphoblastoid cell line (RPMI-8866), natural killer cell stimulatory factor (NKSF), on NK and antibody-dependent cellular cytotoxicity (ADCC) of human colon adenocarcinoma cell lines. Human peripheral blood lymphocytes were cultured for 24 hr in the presence or absence of NKSF (3.6 pM) or interleukin-2 (1 nM). The cultured lymphocytes were analyzed for lytic potential toward chromium-51-labeled colon carcinoma targets SW 1116, 498 LI, and WC 1. ADCC was measured by incubating chromium-51-labeled SW 1116 or WC 1 targets with the monoclonal antibody CO17-1A, an IgG2a antibody reactive with gastrointestinal cancer-associated cell antigen, or control mouse IgG prior to testing NKSF-treated or control PBL effectors in a 6-hr cytotoxicity assay. NKSF significantly enhanced NK cytolysis of colon carcinoma and NK-resistant lymphoma cell lines, and on a molar basis was approximately 300 times more potent than interleukin-2 in generating NK cytotoxicity. Furthermore, NKSF significantly augmented lymphocyte-mediated ADCC against colon carcinoma targets, and the combination of NKSF with the antibody CO17-1A had an additive effect on lymphocyte tumoricidial capacity. Thus, NKSF may have a potential role in the treatment of colon cancer.     

Natural killer cell activity after immediate postoperative enteral and parenteral nutrition

Effects of immediate postoperative enteral and parenteral nutrition on natural killer (NK) cell activity were compared after major abdominal surgery. Eleven patients were fed enterally (2,000 kcal/12.4 g N) and eleven parenterally (1,940 kcal/12.4 g N) for three days after operation. NK cell activity against K562 target cells, determined in the 51Cr release assay, was similar in patients of both groups preoperatively. Postoperatively the patients showed a decrease in NK cell activity (p less than 0.01) but without differences between the groups. The percentages of NK cells did not change between or within the two groups. The results suggest that immediate postoperative enteral nutrition had no superiority over parenteral nutrition on NK cell function in surgical patients.     

Natural killer cells and lung transplantation, roles in rejection, infection, and tolerance

Despite improvements in surgical technique, organ preservation, immunosuppression, and management of infection, the long term survival following lung transplantation remains low, mainly due to immune mediated complications such as acute and chronic rejection. Almost all immunosuppressive agents used in the prophylaxis and treatment of rejection following lung transplantation are targets of T cell maturation, function or proliferation, which in theory should cause sufficient disruption of the adaptive immune system to prevent graft rejection. However the five year survival rate of only 50% suggests this is not the case. More recent evidence suggests that NK cells may play a significant role in immune processes following lung transplantation. This article reviews the literature on the potential function of NK cells in rejection, infection, malignancy and tolerance following lung transplantation.     

Natural killer cell function predicts severe infection in kidney transplant recipients

The aim of this study was to determine if natural killer cell number (CD3^?/CD16^±/CD56^±) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty‐nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74‐0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93‐1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.     

Increase in natural killer cell activity following living-related liver transplantation

Abstract We monitored the serial changes of natural killer cell (NK) activity in eight recipients of living-related liver transplantation. The HLA types of all eight patients were haplotypically identical with those of their donors. Tacrolimus and methylprednisolone were used for immunosuppression. The NK activity before transplantation was 24.1 ± 20.2 % which is surprisingly low when compared with the value for normal individuals (67.7 ± 13.2%, P < 0.01) or a liver dysfunction group (49.4 ± 21.9%, P < 0.05). Serial changes in NK activity revealed a minimum of 6.1 ± 3.6% 1 week after transplantation, gradually increasing to 49.2 ± 12.5 % at 2 months after transplantation. These results suggest that the diseased liver might play an important role in the suppression of NK activity.