Functional p75 interleukin-2 receptor expression on the fresh blast cells in childhood acute lymphoblastic leukemia with natural killer cell properties

Neoplastic cells of childhood acute lymphoblastic leukemia (ALL) with natural killer (NK) cell properties were studied for the expression of p75 interleukin-2 receptors (IL-2R) and the receptor functions. Freshly prepared blast cells from a patient with ALL had NK cell properties: (1) the phenotype such as CD56+, CD2+, E-rosette+, CD3-, and CD19-; and (2) the presence of spontaneous cytotoxicity against NK-sensitive K562 target cells. Although p55 Tac antigen was not detectable, there was the expression of p75 IL-2R on the freshly prepared blast cells: 70% of the cells reacted with Mik-beta 1 monoclonal antibody against p75 IL-2R as determined by flow cytometry. Two-color flow cytometry revealed that the blast cells expressed both p75 IL-2R and NKH-1. NK activity of the blast cells was augmented by their treatment with 1,000 U/ml recombinant IL-2 (rIL-2): the cytotoxicity level as percentage lysis increased to 38.7% from 22.0% when the normal lymphocyte value increased to 62.1% from 46.2%. Although the blast cells possessed no apparent level of proliferative capacity, the addition of 1,000 U/ml rIL-2 yielded a 2.7-fold increase in their thymidine uptake. These results demonstrate the expression of functional p75 IL-2R on the patient's blast cells with NK cell properties.     

Interleukin 2 receptor bearing T lymphocytes in patients with chronic liver disease

We investigated the role of interleukin 2 receptor expression (IL 2R) on T cell in chronic liver disease. IL 2R was determined by analysing T cell surface Tac antigen with anti-Tac, a monoclonal antibody that binds at or near the binding site for IL 2, using a fluorescence-activated cell sorter. The percentage of Tac⁺ cells in T cell fraction from peripheral blood mononuclear cells in unstimulated cultures was 7.9 ±2.1% (±SD) in controls. A similar value was obtained in asymptomatic carriers of HBsAg (ASC), in patients with chronic active hepatitis (CAH) and liver cirrhosis (LC). Upon stimulatin with recombinant IL 2, there was a small but significant increase in Tac⁺ cells. The percentages of Tac⁺ cells in IL 2-stimulated cultures were significantly lower in ASC (P<0.01), patients with CAH (P<0.01) and LC (P<0.05) as compared to controls (16.4 ±4.4%). Percentages of Tac⁺ cells after stimulation with phytohemagglutinin P (PHA-P) in ASC and CAH did not differ from controls (74.9 ±5.9%). Only patients with LC showed diminished Tac⁺ cells (P<0.01) compared to controls. During a 4-wk course of recombinant IL 2 therapy, a serial study on 5 HBeAg-positive patients with CAH was done, and the results showed that Tac⁺ cells were significantly diminished 2 wk (P<0.01) and 4 wk (P<0.05) after starting therapy in comparison with pretreatment levels in IL 2-stimulated cultures. OKT3⁺, OKT4⁺, OKT8⁺ cells in T cell culture in response to stimulation with PHA-P were significantly decreased in patients with CAH and LC when compared with controls. These results indicate that IL 2/ IL 2R system has a role on modulating immune resoponse in chronic liver disease.     

Increased serum levels of β2m-free HLA class I heavy chain in multiple myeloma

Serum levels of beta2-microglobulin (beta2m)-free HLA class I heavy chain (FHC) in 94 patients with multiple myeloma (MM) were higher than in 29 patients with monoclonal gammopathy of undetermined significance (MGUS) (P = 0.023) and in 97 sex- and age-matched healthy controls (P < 0.0001). Spearman correlation analysis indicated that in MM, FHC correlated with beta2m (r = 0.31, P = 0. 003) and the percentage of bone marrow plasma cells (BMPC%) (r = 0. 36, P = 0.002), whereas beta2m, in addition to BMPC% (r = 0.43, P = 0.0003), also correlated with creatinine levels (r = 0.63, P < 0.0001), haemoglobin levels (r = -0.35, P = 0.0007) and patient age (r = 0.34, P < 0.0011). Furthermore, MM patients with poor prognosis (beta2m >/= 6 mg/l) displayed higher FHC levels than those with a better prognosis (beta2m < 6mg/l) (P < 0.021). At variance from beta2m, these levels were not influenced by renal failure, as indicated by the lack of Spearman correlation of FHC with creatinine concentration and of statistical significance between the median FHC concentration of MM patients with creatinine < 176.6 micromol/l and those with creatinine >/= 176.6 micromol/l (P = 0.3). Stratification of patients according to disease activity and stage showed that FHC levels were only statistically different (P = 0.04) for disease activity, whereas beta2m and C-reactive protein were not. Taken together, our data indicate that serum FHC may be a useful disease marker in MM.     

Reduced production of immunoreactive interleukin-1 by peripheral blood monocytes of patients with acute and chronic viral hepatitis

The in vitro production of interleukin-1 by peripheral blood monocytes derived from patients with various liver diseases was studied. An impaired production of immunoreactive interleukin-1 (IL-1) (mean±sem) by monocytes stimulated, with an optimal dose (100 ng/ml) of lipopolysaccharide was observed in patients with chronic hepatitis B (N= 13; 32±6 pg/ml) or chronic hepatitis C (N= 13; 61±12pg/ml) as compared to those of healthy control individuals (N=35; 166±24 pg/ml;P=0.0003 andP=0.015, respectively), whereas an unaltered, IL-1 production was seen in patients with alcoholic cirrhosis (N=23; 125±28 pg/ml) and primary biliary cirrhosis (N=6; 111±33pg/ml) Similar to the situation seen in chronic viral hepatitis, lipopolysaccharide-stimulated monocytes from patients with acute hepatitis also showed a decreased IL-1 production in the first week after onset of jaundice (N=17; 55±20 pg/ml;P=0.001) and a return to normal in the second and third week. An impaired production of IL-1 in chronic as well as acute viral hepatitis is a further example of the known disturbed immunoregulation in this disease.     

外周血淋巴细胞亚群在慢性HBV感染过程中表达的变化分析

目的探讨HBV感染患者外周血淋巴细胞亚群在疾病进展过程中的表达变化。方法选取2018年1月-2019年4月在天津市第二人民医院住院的慢性HBV感染患者共132例,其中慢性乙型肝炎患者47例,乙型肝炎肝硬化患者44例,乙型肝炎肝硬化相关原发性肝癌患者41例。另选取同期健康体检者42例作为对照组。采用流式细胞术检测4组外周血淋巴细胞亚群精准计数,比较4组外周血淋巴细胞亚群的表达水平。正态分布的计量资料,组间方差不齐采用Welch方差分析,两两比较采用GamesHowell检验。非正态分布的计量资料多组间及进一步两两比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。相关性分析采用Spearman检验。结果与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD3^+、CD4^+T淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组相比,肝癌组CD8^+T淋巴细胞数量明显减少,差异有统计学意义(P<0.05);与慢性乙型肝炎组相比,肝硬化组和肝癌组CD8^+T淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD19^+B淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组相比,肝硬化组和肝癌组CD16^+CD56^+NK细胞数量明显减少,差异均有统计学意义(P值均<0.05);与慢性乙型肝炎组比较,肝癌组CD16^+CD56^+NK细胞数量明显减少,差异有统计学意义(P<0.05)。4组疾病进展与外周血CD3^+T淋巴细胞、CD4^+T淋巴细胞、CD8^+T淋巴细胞、CD19^+B淋巴细胞、CD16^+CD56^+NK细胞呈明显负相关(r值分别为-0.414、-0.503、-0.269、-0.435、-0.402,P值均<0.01)。结论随着疾病的进展,慢性HBV感染患者免疫状态发生变化。外周血淋巴细胞亚群精准计数能够反应机体的免疫状态,可作为慢性HBV感染临床病情演变、治疗效果及疾病预后的参考依据。     

Anaemia of chronic disease in AA amyloidosis is associated with allele 2 of the interleukin-1beta-511 promoter gene and raised levels of interleukin-1beta and interleukin-18

OBJECTIVE: In amyloid A (AA) amyloidosis the receptor for advanced glycation end products is a target for the circulating amyloid precursor protein (SAA) resulting in upregulation of the proinflammatory cytokine pathway. Besides inducing hepatic SAA synthesis the interleukin-1 cytokine family is involved in the regulation of haematopoiesis. We therefore studied the relationship between the circulating levels of interleukin-1beta (IL-1beta) and interleukin-18 (IL-18), a new member of the IL-1 complex, as well as polymorphisms within the IL-1 cluster with the occurrence of anaemia in patients with AA amyloidosis. DESIGN, SETTING AND SUBJECTS: The study included 54 adult patients with biopsy-proven reactive amyloidosis allocated into three groups on the basis of haemoglobin (Hb) level: group I included all patients with Hb < 110 g L(-1) (n = 16); group II patients (Hb > 110 g L(-1), n = 16) were selected to match group I patients with respect to sex, age, underlying disease (seropositive, erosive rheumatoid arthritis) and renal function; and group III patients (n = 38) represented all patients (unselected) with Hb > or = 110 g L(-1). Gene polymorphisms were studied by polymerase chain reaction restriction length assay and included the base exchange at position-889 of the IL-1alpha gene, the polymorphic region at position-511 and the polymorphic locus at exon 5, position +3954 of the IL-1beta gene, as well as the IL-1 receptor antagonist (IL-1Ra) exon 2 polymorphism caused by the 86-bp tandem repeats. Plasma IL-1beta, IL-1alpha, IL-18, IL-1 Ra, SAA, ferritin, soluble transferrin receptor and erythropoietin levels were studied by enzyme immunoassays. RESULTS: Circulating IL-beta and IL-18 were significantly raised in the anaemic patients with AA amyloidosis when compared with group II patients (matched, Hb > 110 g L(-1)) as well as group III patients (nonmatched, Hb > or = 110 g L(-1)). A significant inverse relationship was found between IL-1beta and haemoglobin levels, as well as between IL-18 and haemoglobin levels. The frequency of allele 2 (T) of the IL-1beta-511 promoter gene was significantly increased and that of allele 1 (C) decreased in anaemic amyloid patients (group I) when compared with group II and III patients. Circulating IL-1beta levels tended to be higher amongst the IL-1beta-511 allele 2 carriers than amongst the noncarriers, as well as amongst the anaemic amyloid patients filling all criteria of anaemia of chronic disease. CONCLUSION: The occurrence of anaemia in patients with AA amyloidosis is associated with allele 2 (T) of the IL-1beta-511 promoter gene and elevated levels of circulating IL-1beta and IL-18. In AA amyloidosis the raised cytokine levels may generate a vicious cycle leading to accelerated amyloidogenesis, suppression of erythropoiesis and aggravation of the underlying inflammatory disorder.     

Involvement of endogenous nitric oxide in the inhibition by endotoxin and interleukin-1β of gastric acid secretion

Abstract Administration of Escherichia coli endotoxin abolished the acid secretory response induced by a bolus injection of pentagastrin in the continuously perfused stomach of the anaesthetized rat. Likewise, acid secretion stimulated by the continuous intravenous perfusion of pentagastrin was inhibited by administration of interleukin-1β (IL-1β). In both cases pretreatment with N ^g-nitro- l -arginine methyl ester ( l -Name) but not dexamethasone or indomethacin substantially restored the secretory responses to pentagastrin. The actions of l -Name were reversed by the prior administration of l -arginine but not by its enantiomer d-arginine. Even though l -Name increased blood pressure, this does not seem to be the mechanism by which endotoxin-induced acid inhibition was prevented, since similar systemic pressor responses induced by phenylephrine had no such effect. The secretory response elicited by pentagastrin in the isolated lumen perfused stomach of the rat was not influenced by incubation (100 min) with IL-1β. These observations suggest that the acute inhibition of acid responses to pentagastrin by endotoxin and IL-1β involves nitric oxide (NO) synthesis from l -arginine.     

Natural killer cell activity in patients with liver cirrhosis relative to severity of liver damage

To evaluate the role of severe liver damage on natural killer cell activity, 29 patients with liver cirrhosis were examined. The natural killer cell activity was measured with a 4-hr chromium release assay, and the K562 cell line was employed as target cells. The natural killer cell activity was significantly decreased in cirrhotic patients compared with normal controls and patients with chronic active hepatitis. Cirrhotic patients with Pugh's C grade of severity of liver disease had lower natural killer cell activity. The depression of natural killer cell activity in cirrhotic patients was inversely correlated with prothrombin time ratios, and the natural killer cell activity in cirrhotic patients with hepatic encephalopathy was lower than in patients without hepatic encephalopathy. Thus, the diminished natural killer cell activity in cirrhotic patients might be related to the severity of liver damage.     

外周血白细胞介素32和金属基质蛋白酶-2对HBV相关慢加急性肝衰竭预后的预测价值研究

目的探讨外周血白细胞介素(interleukin,IL)-32和金属蛋白酶(matrix metalloproteinases,MMP)-2表达水平对HBV相关慢加急性肝衰竭(HBV-associated acute-on-chronic liver failure,HBV-ACLF)预后的预测价值。方法选择34例HBV-ACLF和31例慢性乙型肝炎(chronic hepatitis B,CHB)患者作为研究对象,检测外周血IL-32和MMP-2的表达水平,并与ALT、AST、TBIL、ALB及PT等指标进行相关性分析;采用Logisitic回归分析IL-32和MMP-2预测HBV-ACLF预后的价值。结果 HBV-ACLF组IL-32与TBIL、PT呈中等程度正相关(r_s=0.774、0.686),与ALB呈弱负相关(r_s=-0.456);MMP-2与ALB呈弱负相关(r_s=-0.451);IL-32与MMP-2呈弱正相关(r_s=0.580)。CHB组IL-32与TBIL、PT呈弱正相关(r_s=0.439、0.555);MMP-2与AST呈弱正相关(r_s=0.417),与ALB呈弱负相关(r_s=-0.541),与TBIL、PT呈中等程度正相关(r_s=0.647、0.766);IL-32与MMP-2呈弱正相关(r_s=0.590)。HBV-ACLF组、CHB组和对照组外周血IL-32表达水平呈依次升高(P均0.05)。HBV-ACLF组MMP-2表达高于CHB组和对照组(P均0.05),但CHB组与对照组相比,差异无统计学意义。在合并感染率、外周血IL-32和MMP-2表达水平方面,HBV-ACLF组明显高于CHB组。Logisitic回归分析发现IL-32与HBV-ACLF的预后密切相关。结论外周血IL-32和MMP-2的表达水平可反映肝损伤严重程度;IL-32与HBV-ACLF的预后密切相关。     

Depressed NK cell activity of peripheral blood mononuclear cells in untreated Hodgkin's disease: Enhancing effect of interferon in vitro

Natural killer (NK) cell activity of unseparated peripheral blood mononuclear cells from 30 untreated patients with Hodgkin's disease and 22 age- and sex-matched normal controls was evaluated using the classical K 562 cells as targets. A significant defect was demonstrated in the patients with stage I-II and seemed to be more profound in patients with advanced disease (stage III-IV) and in those with B symptoms. The differences between subgroups of patients, however, were not statistically significant, mostly because of the wide dispersion of individual data. Pre-incubation of effector cells with alpha A leucocyte recombinant interferon led to a clear increase in NK cell activity in 4 of 6 patients tested, showing that depressed NK activity in Hodgkin's disease is still susceptible to the enhancing effect of interferon, at least in some patients.—     

Second transplantation using allogeneic peripheral blood stem cells in a β-thalassaemia major patient featuring stable mixed chimaerism

Allogeneic bone marrow transplantation (BMT) for β-thalassaemia major carries the risks of disease recurrence due to residual thalassaemic stem cells or true immune-mediated rejection. We report a thalassaemic patient who displayed stable mixed chimaerism with only 5% donor-derived cells for about 5 years after BMT. Displacement of host cells was accomplished by ambulatory non-myeloablative conditioning and allogeneic G-CSF mobilized peripheral blood stem cell transplantation from the same donor, resulting in full reconstitution. Patients featuring stable mixed chimaerism after BMT may benefit from allogeneic cell therapy with immunocompetent lymphocytes and stem cells, whilst avoiding supralethal conditioning.     

肝舒胶囊对慢性肝炎患者免疫功能的影响

为探讨肝舒胶囊对慢性肝炎患者免疫功能的调节作用，检测了肝舒胶囊治疗前后慢性肝炎患者的T淋巴细胞亚群、自然杀伤细胞及血清可溶性白细胞介素-2受体（sIL-2R）等指标，并以健康献血者为对照。结果肝炎组CD、CD、CD／CD、CD及CD显著下降（P＜0.01），CD、sIL-2R显著增高（P＜0．01），经过肝舒胶囊治疗后，呈相对应负性改变（P＜0．05）。提示肝舒胶囊对免疫功能有显著改善和调节作用。     

乙型肝炎肝硬化患者外周血自然杀伤细胞频率、功能及其受体表达的变化

目的调查乙型肝炎肝硬化患者外周血自然杀伤细胞(NK细胞)频率、功能及受体表达的变化。方法收集2013年6月-2014年12月解放军第三○二医院收治的乙型肝炎肝硬化患者34例作为肝硬化组,另收集30例健康献血者为健康对照组,用流式细胞仪分析两组外周血NK细胞频率及其受体CD158a、CD158b、NKG2D、NKP30、NKP44、NKP46的表达情况,用白细胞介素(IL)12刺激外周血单个核细胞、流式细胞术检测NK细胞分泌干扰素(IFN)γ和肿瘤坏死因子(TNF)α的能力,并用流式细胞分析法检测NK细胞对K562细胞的杀伤效率,对两组NK细胞频率、受体表达及功能进行分析和比较。正态分布资料两组间比较采用t检验,非正态分布资料两组间比较采用Mann-Whitney U检验。结果 CD56dimNK细胞频率肝硬化组低于健康对照组,差异有统计学意义(Z=-2.309,P0.05),CD56brightNK细胞频率肝硬化组高于健康对照组,差异有统计学意义(Z=2.395,P0.05)。CD56dimNK细胞的活化性受体NKP44、NKP46表达率肝硬化组高于健康对照组,差异均有统计学意义(Z值分别为2.834、3.404,P值均0.05)。CD56brightNK细胞的受体NKP30、NKP44、NKP46表达率肝硬化组高于健康对照组,差异均有统计学意义(Z值分别为3.518、4.003、4.480,P值均0.05)。在IL-12刺激下肝硬化组CD56dimNK细胞TNFα表达率低于健康对照组,差异有统计学意义(Z=-3.510,P0.05),CD56brightNK细胞IFNγ表达率低于健康对照组,差异有统计学意义(Z=-4.301,P0.05)。肝硬化组NK细胞对K562细胞的杀伤比例在效靶比3∶1、10∶1、30∶1时均低于健康对照组,差异均有统计学意义(Z值分别为-2.355、-2.523、-2.523,P值均0.05)。结论肝硬化患者NK细胞功能下降,可能与CD56dimNK细胞频率减低,细胞因子分泌下降有关,与受体表达无关。     

Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft-versus-host disease

Acute graft-versus-host disease (aGVHD) occurs in up to 80% of patients who undergo allogeneic stem cell transplantation (SCT) and contributes significantly to transplant-related mortality (TRM). We conducted a prospective phase II trial to assess the efficacy and feasibility of treating steroid-refractory aGVHD with basiliximab, a chimaeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor. Basiliximab was administered intravenously at a dose of 20 mg on days 1 and 4. Twenty-three patients were enrolled between October 1999 and July 2004. We found a primary overall response rate of 82.5% with four patients (17.5%) showing a complete response and 15 patients (65%) a partial response. Six patients were again treated successfully with an IL-2 receptor antagonist because of recurrence of aGVHD. The rates of infections, chronic GVHD, malignancy recurrence and 1-year TRM following immunosuppression with basiliximab were comparable with those found with other treatment modalities for aGVHD. We conclude that basiliximab is efficient and feasible for steroid-refractory aGVHD and merits further evaluation.     

An insight into the protection of rat liver against ischemia/reperfusion injury by 2-selenium-bridged β-cyclodextrin

Aim:  The reperfusion following liver ischemia results in the damage and apoptosis of hepatocytes. The aim of this study was to investigate the possible effects and mechanism of a new synthesized glutathione peroxidase (GPX) mimic, 2-selenium-bridged β-cyclodextrin (2-SeCD), on rat liver ischemia-reperfusion (I/R) injury.
Methods:  Male Wistar rats ( n  = 32) were randomly divided into four groups: I. sham-operated group, II. I/R group, III. I/R +2-SeCD group, IV. I/R + Ebselen group. Hepatic I/R was administered by 90 min of ischemia and 12 h of reperfusion. Liver tissues were collected at the end of reperfusion period for measurement of various biochemical parameters.
Results:  The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) activity and tissue malondialdehyde, myeloperoxidase levels were increased in I/R group, while the increase was significantly reduced by 2-SeCD treatment. The glutathione level, depressed by I/R, was elevated back to normal levels by treatment with 2-SeCD. Severe hepatic damage were observed by light and transmission electron microscopy whilst pretreatment with 2-SeCD resulted in tissue and cellular preservation. Furthermore, 2-SeCD reduced cytochrome c release from mitochondria and subsequent DNA fragmentation by regulating Bcl-2/Bax expression ratio. Results suggested that 2-SeCD was more effective than ebselen in the reversal of the alteration in tissue structural and biochemical parameters caused by I/R injury.
Conclusion:  2-selenium-bridged β-cyclodextrin playes an important role in the protection of liver against I/R injury and this treatment may be a novel pharmacological agent for liver surgery.     

乙型肝炎相关慢加急性肝衰竭患者血清白细胞介素1受体拮抗剂与疾病严重程度的关系

目的探讨乙型肝炎相关慢加急性肝衰竭(HBV-ACLF)患者外周血白细胞介素(IL)1受体拮抗剂(IL-1Ra)与患者疾病严重程度的关系。方法选取福州市传染病医院2013年10月-2015年1月就诊的31例HBV-ACLF患者为研究对象,另选取同期28例急性乙型肝炎(AHB)和30例慢性乙型肝炎(CHB)患者作为对照。用Q-Plex法检测外周血IL-1Ra、IL-1β、IL-6、IL-4、IL-10、肿瘤坏死因子(TNF)α、干扰素(IFN)γ等细胞因子浓度,并检测各组肝功能、凝血功能等,将血清IL-1Ra等细胞因子浓度与患者肝功能、MELD评分及HBV DNA等进行相关分析。多组间比较采用Kruskal-wallis H检验,进一步两两比较采用Mann-Whitney U检验;计数资料采用χ2检验;相关分析采用Spearman秩相关。结果 IL-1Ra、IL-1Ra/IL-1β在3组之间的差异均有统计学意义(P值均0.05),其中HBV-ACLF组IL-1Ra水平[186.46(162.68~512.90)pg/ml]显著高于CHB组[70.47(47.07~92.47)pg/ml]和AHB组[143.69(117.75~208.54)pg/ml],差异均有统计学意义(Z=6.300,P0.001;Z=2.505,P=0.012);而HBV-ACLF患者IL-1Ra与IL-1β比值[2.92(2.20~4.74)]较AHB组[4.54(2.75~6.05)]低,但较CHB患者[2.49(1.50~2.50)]高,差异均有统计学意义(Z=1.966,P=0.048;Z=2.682,P0.001)。HBV-ACLF组IL-1β、IL-6、TNFα水平显著高于其他2组(P值均0.01)。血清IL-1Ra与TBil、MELD评分均呈负相关(r值分别为-0.506、-0.818,P值均0.01),与凝血酶原活动度(PTA)呈正相关(r=0.475,P=0.007)。结论 IL-1Ra与反映HBV-ACLF严重程度的指标TBil、MELD评分呈负相关,与PTA呈正相关,IL-1ra在HBV-ACLF发病过程中可能起重要作用。     

Decreased expression of the interleukin 2 receptor on CD8 recipient lymphocytes in intestinal grafts rendered tolerant by liver transplantation in rats

Background—In a previous study, it was shown thata spontaneously tolerated DA (RT1a) liver allograft in a PVG (RT1c)recipient was able to induce tolerance of a DA small bowel graftperformed 17 days later in spite of infiltration of the intestinalgrafts by mononuclear cells.
Aims—To compare the phenotype of graftinfiltrating cells in rejecting and tolerated small bowel grafts inorder to elucidate the mechanism(s) which block the graft infiltratingcells from mediating rejection.
Methods—Multiparameter immunofluorescence wasused to compare the phenotype and state of activation of donor andrecipient cells isolated from intestinal grafts rejected or toleratedafter liver transplantation.
Results—Three differences were found. Firstly,there was a more rapid replacement of lamina propria (LP) cells byrecipient lymphocytes in tolerated than in rejected grafts. Secondly,the proportion of LP recipient CD8αβ+ lymphocytes bearing the high affinity receptor for interleukin 2 was significantly less in toleratedgrafts (1.1%, range 0-2%) than in rejected grafts (21.3%, range9-26%). Finally, tolerated grafts contained significantly less NKlymphocytes (NKR-P1+) and macrophages than rejected intestinal allografts.
Conclusions—These observations make it possibleto delineate clear cut differences in the phenotype of cellsinfiltrating rejecting versus tolerated grafts. Furthermore, the datasuggest that liver transplantation induces tolerance of intestinalgrafts by hampering the activation of recipient TcRαβ+ CD8αβ+ Tcells and subsequently the recruitment of non-specific effector cells.

Keywords:liver transplantation; small bowel transplantation; tolerance; intestinal T lymphocytes; interleukin 2 receptor; rat