CD4/CD8 T‐Cell Ratio in Peritoneal Dialysis Effluents Predicts the Outcome of Peritonitis in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

This study aimed to clarify the role of peritoneal T‐lymphocytes in peritoneal immune defense mechanisms. This study was designed to examine the changes in T‐cell subpopulations during peritonitis in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Our observations were correlated to responses to treatment and with outcomes. The present study was carried out in 20 patients (8 males, 12 females) under CAPD. Peritonitis was diagnosed according to the criteria defined by the Ad Hoc Advisory Committee on Peritonitis Management. Peritoneal dialysate effluent (PDE) samples were collected from our patients, and lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD3?/16+56+, CD4/CD8 ratio) were quantitated by using monoclonal antibodies. CD4/CD8 ratio was measured every day during peritonitis until the patients had completely recovered. The serial measurements of the CD4/CD8 ratio made in the PDE during peritonitis followed two patterns: the first pattern was characterized by a progressive increase in the CD4/CD8 ratio. The CD4/CD8 ratios on days 5, 6, and 7 were significantly higher than those on day 1 (P < 0.05). Overall, the patients who exhibited pattern 1 had favorable clinical courses. The second pattern was characterized by high initial CD4/CD8 ratios, which progressively decreased significantly (P < 0.05). This second pattern was associated with a delayed clinical response to treatment. Symptoms and signs of peritonitis persisted beyond 72 h. The pattern of the CD4/CD8 ratio in PDE may determine the outcome of peritonitis in CAPD patients.     

Growth factors in continuous ambulatory peritoneal dialysis effluent. Their relation with peritoneal transport of small solutes.

Recent studies reveal conflicting results on the change of solute transfer with time on continuous ambulatory peritoneal dialysis (CAPD) and recurrent peritonitis. Herein, we performed a cross-sectional study of 76 patients on CAPD to examine their peritoneal permeability by measuring the dialysate to serum ratio of creatinine (D/P) and the mass transfer area coefficients of creatinine (MTACCr) or glucose (MTACGlu). Transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) were measured in the dialysate by ELISA. TGF-beta1 mRNA in peritoneal macrophages were determined by a quantitative polymerase chain reaction. We failed to observe any correlation between the duration on dialysis and the peritoneal permeability in those patients with no previous peritonitis. Frequency of peritonitis episode did not affect the MTACCr, MTACGlu, or D/P. The MTACCr correlated well with MTACGlu (r = 0.78, p = 0. 001) and with D/P (r = 0.98, p < 0.0001). No inverse correlation was demonstrated between dialysate PDGF or EGF and the peritoneal permeability. A positive correlation was demonstrated between the dialysate TGF-beta1 and MTACCr, MTACGlu or D/P (r = 0.64, 0.54, and 0.64 respectively, p < 0.001). The dialysate TGF-beta1 levels in patients with low D/P (相似文献   

Comparison of blood and peritoneal lymphocytes from continuous ambulatory peritoneal dialysis patients, asymptomatic and with peritonitis

OBJECTIVE: The purpose of this study was to compare the characteristics of the blood immunophenotype of CAPD patients with and without peritonitis and to compare the phenotypes of peripheral blood lymphocytes (PBL) and peritoneal lymphocytes (PL) in CAPD patients with peritonitis. METHODS: Fifty-seven CAPD patients (20 with peritonitis and 37 without peritonitis) were recruited in the study (mean age 66,88 +/- 13,48, male/ female 16/21). Lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD3-/16 + 56+, CD4/CD8 ratio) were quantitated by using monoclonal antibodies and dual-color flow cytometric analysis. With the above method we measured PBL in patients with and without peritonitis. In patients with peritonitis we also measured PL. RESULTS: CD2 were slightly decreased in patients with peritonitis. Those patients also had more intense CD3 + / CD4+ lymphopenia (p < 0.05) and larger expansion of NK cells (p < 0.05). Patients with peritonitis appeared to have a lower ratio of CD4/CD8 (p < 0.05). All the above results are shown to Table 2. Following the onset of peritonitis, a consistent finding in all patients was a significant increase in CD2 population of PL compared with PBL (85.71 +/- 9.20 versus 82.60 +/- 7.34, p < 0.05) as well as in CD3 population (77.01 +/- 13.09 versus 68.74 +/- 13.43, p < 0.05). An increased number of CD3/8 in PL compared with PBL (33.70 +/- 9.34 versus 27.98 +/- 10.77, p < 0.05) was also noted. CONCLUSIONS: In the present study, we found important immune activation in asymptomatic CAPD patients. The activation increases during peritonitis. The causes and the clinical consequences of chronic activation remain unknown.     

Intraperitoneal secretion of interleukin-6 during continuous ambulatory peritoneal dialysis

Interleukin-6 (IL-6) was determined in serum and peritoneal dialysis effluent (PDE) of patients on chronic ambulatory peritoneal dialysis (CAPD) by a biological assay measuring the proliferation of the IL-6-dependent 7TD1 cell line. Six patients free of peritonitis displayed low but significant levels of IL-6 (mean +/- 42 pg/ml) in PDE, while IL-6 was undetectable in serum. In 6 patients with staphylococcal peritonitis, a tremendous increase in PDE levels of IL-6 was noted (range: 5,832-37,491 pg/ml), while serum IL-6 remained either undetectable or on a low level except in one case. After 5 days of antibiotic treatment, IL-6 levels in PDE returned to basal values. We conclude that CAPD results in an intraperitoneal secretion of IL-6 which is markedly but transiently increased during peritonitis episodes.     

Monitoring of Human Cytomegalovirus-Specific CD4+ and CD8+ T-Cell Immunity in Patients Receiving Solid Organ Transplantation

Absolute and human cytomegalovirus (HCMV)-specific CD4+ and CD8+ T-cell counts were monitored in 38 solid organ (20 heart, 9 lung and 9 kidney) transplant recipients during the first year after transplantation by a novel assay based on T-cell stimulation with HCMV-infected autologous dendritic cells. According to the pattern of T-cell restoration occurring either within the first month after transplantation or later, patients were classified as either early (n = 21) or late responders (n = 17). HCMV-specific CD4+ and CD8+ T-cell counts were consistently lower in late compared to early responders from baseline through 6 months after transplantation. In addition, in late responders, while HCMV infection preceded immune restoration, HCMV-specific CD4+ restoration was significantly delayed with respect to CD8+ T-cell restoration. The number of HCMV-specific CD4+ and CD8+ T-cells detected prior to transplantation significantly correlated with time to T-cell immunity restoration, in that higher HCMV-specific T-cell counts predicted earlier immune restoration. Clinically, the great majority of early responders (18/21, 85.7%) underwent self-resolving HCMV infections (p = 0.004), whereas the great majority of late responders (13/17, 76.5%) were affected by HCMV infections requiring antiviral treatment (p = <0.0001). Simultaneous monitoring of HCMV infection and HCMV-specific T-cell immunity predicts T-cell-mediated control of HCMV infection.     

Longitudinal changes of solute transport in peritonitis-free peritoneal dialysis patients

BACKGROUND: The aim of this study was to evaluate the longitudinal changes in peritoneal transport in patients on long-term, peritonitis-free, continuous ambulatory peritoneal dialysis (CAPD) therapy. METHODS: Results were longitudinally recorded for the standard peritoneal equilibration test (PET) in 76 consecutive, nondiabetic, adult patients from the beginning of CAPD therapy until their first episodes of peritonitis, abdominal surgery, or any cause of drop out. The PET results were evaluated once annually using the dialysate-to-plasma ratio of creati-nine (D/PCr) and the dialysate-to-instilled dextrose ratio (D4/D0) at 4 hours after beginning dialysis. RESULTS: A total of 168 PET results were obtained. A statistically significant tendency toward decreased D/PCr and increased D4/D0 values over time for up to 3 years was found. CONCLUSIONS: This study shows a tendency toward progressive decline in small molecular transport over time in nondiabetic patients with uneventful CAPD therapy. Sequential PET follow-up cannot be overlooked in peritonitis-free CAPD patients.     

Down-regulation of CD43 molecule expression on intraperitoneal neutrophils in CAPD patients with peritonitis

To assess the release of proteases from neutrophils infiltrated into the peritoneal cavity in continuous ambulatory peritoneal dialysis (CAPD), we investigated the regulation of CD43, LAM-1 and Mac-1 expression on the neutrophil plasma membrane using FACS analysis in CAPD patients with peritonitis. Five CAPD patients with peritonitis and five CAPD patients without peritonitis were studied. CD43 expression was immunohistochemically determined in both groups of patients using flow cytometry, and comparisons were made between the two groups. Down-regulation of CD43 and LAM-1, and up-regulation of Mac-1 were demonstrated on neutrophils obtained from CAPD dialysate of peritonitis patients after 1-h dwell time. Further up-regulation of Mac-1 developed until a dwell time of 4 h. Immunoblot analysis for neutrophil lysate from dialysate showed the presence of the asialo form of CD43 molecules and their fragments, which may be produced by cleavage of the CD43 molecule at extracellular sites. The intraperitoneal neutrophils in dialysate from CAPD patients with peritonitis are continuously activated during dwell time, and proteases may be released from neutrophils into dialysate after only a short dwell time.     

Peritoneal fluid and solute transport: influence of treatment time, peritoneal dialysis modality, and peritonitis incidence

The integrity of the peritoneal membrane in peritoneal dialysis (PD) is of major importance for adequate dialysis and fluid balance. However, alterations in peritoneal fluid transport, such as ultrafiltration failure, often develop during long-term PD. To investigate peritoneal solute and fluid transport and to analyze the influence of treatment time, peritonitis incidence, and PD modality (continuous ambulatory PD [CAPD] or automated PD [APD]), a cross-sectional study with an extended peritoneal transport test that used dextran 70 in 2 L of glucose was performed in 23 nonselected chronic PD patients. Compared were long-term (>40 mo) with short-term PD patients (<40 mo), CAPD with APD patients, and those with a peritonitis incidence of >0.25/yr to those with an incidence of <0.25/yr. Dialysate/plasma (D/P) ratio and mass transfer area coefficient of creatinine, lymphatic absorption rate (LAR), transcapillary ultrafiltration, and effective ultrafiltration were measured. Long-term PD patients had higher D/P ratio of creatinine (73.5 +/- 2.3% versus 65.9 +/- 2.2%; P < 0.01) and higher LAR (243 +/- 69 ml/4 h versus 96 +/- 31 ml/4 h; P < 0.03), both resulting in lower effective ultrafiltration (242 +/- 35 ml/4 h versus 324 +/- 30 ml/4 h; P < 0.05). D/P ratio (r = 0.66) and LAR (r = 0.67) were positively correlated to PD duration. Patients on APD compared with those on CAPD and patients with a history of peritonitis compared with those without did not differ in terms of D/P ratio, mass transfer area coefficient, LAR, transcapillary ultrafiltration, and effective ultrafiltration. Lower ultrafiltration after long-term PD is both the result of increased small solute transport and increased lymphatic absorption. APD or CAPD modality and peritonitis incidence do not have a significant influence on small solute transport or fluid kinetics.     

Peritoneal sodium mass removal in continuous ambulatory peritoneal dialysis and automated peritoneal dialysis: influence on blood pressure control.

BACKGROUND/AIM: Sodium and water retention is common in peritoneal dialysis patients and contributes to cardiovascular disease. As peritoneal sodium removal depends partly on dwell time, and automated peritoneal dialysis (APD) often uses short dwell time exchanges, the aim of this study was to compare the 24-hour peritoneal sodium removal in APD and standard continuous ambulatory peritoneal dialysis (CAPD) patients and to analyze its possible influence on blood pressure control. METHODS: A total of 53 sodium balance studies (30 in APD and 23 in CAPD) were performed in 36 stable peritoneal dialysis patients. The 24-hour net removal of sodium was calculated as follows: M = ViCi - VdCd, where Vd is the 24-hour drained volume, Cd is the solute sodium concentration in Vd, Vi is the amount of solution used during a 24-hour period, and Ci is the sodium concentration in Vi. Peritoneal sodium removal was compared between APD and CAPD patients. Residual renal function, serum sodium concentration, daily urinary sodium losses, weekly peritoneal Kt/V and creatinine clearance, 4-hour dialysate/plasma creatinine ratio, proportion of hypertonic solutions, net ultrafiltration, systolic and diastolic blood pressures, and need for antihypertensive therapy were also compared between the groups. RESULTS: Peritoneal sodium removal was higher (p < 0.001) in CAPD than in APD patients. There were no significant differences in residual renal function, serum sodium concentration, urinary sodium losses, peritoneal urea or creatinine clearances, 4-hour dialysate/plasma creatinine ratio, or proportion of hypertonic solutions between groups. The net ultrafiltration was higher in CAPD patients and correlated strongly (r = 0.82; p < 0.001) with peritoneal sodium removal. In APD patients, peritoneal sodium removal increased significantly only in those patients with a second daytime exchange. The systolic blood pressure was higher (p < 0.05) in APD patients, and the proportion of patients with antihypertensive therapy was also higher in APD patients, although no significant relationship between blood pressure values and amount of peritoneal sodium removal was found. CONCLUSIONS: The 24-hour sodium removal is higher in CAPD than in APD patients, and there is a trend towards better hypertension control in CAPD patients. As hypertension control and volume status are important indices of peritoneal dialysis adequacy, our results have to be considered in the choice of the peritoneal dialysis modality.     

Evaluation of continuous ambulatory peritoneal dialysis

This study was undertaken to ascertain whether 19 patients maintained on continuous ambulatory peritoneal dialysis (CAPD) for at least 1 year experienced any deterioration in peritoneal membrane function. Selected serum chemistries and skinfold measurements were also evaluated to determine whether patients dialyzed by CAPD could maintain a normal nutritional status. This study demonstrates that patients maintained on CAPD had stable dialysate protein losses, glucose absorption from the dialysate, and constant urea, creatinine, and sodium removal. When these patients were subdivided by incidence of peritonitis, the group with a lower incidence of peritonitis (one episode every 349 +/- 155 SEM days) showed stable serum protein concentration and improvement in upper arm area whereas the group with a high incidence of peritonitis (one episode every 95 +/- 7 SEM days) showed a reduction in upper arm muscle area. Thus, our data suggest that over a 1-year period, there is no deterioration in peritoneal membrane characteristics and CAPD is effective in maintaining the nutritional status of the patient. However, both membrane function and nutritional status may be impaired by frequent episodes of infection.     

Peritoneal kinetics in children undergoing continuous ambulatory/cycling peritoneal dialysis

We present a report on peritoneal kinetics in children undergoing continuous ambulatory/cycling peritoneal dialysis (CAPD/CCPD). The effect of long-term treatment with CAPD/CCPD, peritonitis episodes, and dialysate inflow volume on peritoneal kinetics in children was evaluated. Peritoneal kinetic studies (PKSs) were performed in 47 pediatric patients at different times following initiation of CAPD/CCPD. In 18 of these patients, PKSs were repeated up to four times with an unchanged dialysate inflow volume after up to 55 months of CAPD/CCPD treatment. The PKS consisted of a 120-minute dwell with a 1.5% dextrose dialysate solution. Peritoneal clearance, dialysance, and dialysate to plasma (D/P) concentration ratios were calculated after 30, 60, and 120 minutes. The results of the serial PKSs demonstrate stable peritoneal creatinine and urea-N clearance, dialysance or D/P concentration ratios. Furthermore, there was no adverse effect of 32 peritonitis episodes. Finally, inflow volumes correlated directly with clearances of creatinine (P less than .01), urea-N (P less than .001), and potassium (P less than .001), and there was an inverse relationship to the D/P concentration ratios of creatinine (P less than .01), urea-N (P less than .01), potassium (P less than .01), and uric acid (P less than .01). Thus, CAPD/CCPD is a useful and effective long-term treatment modality for pediatric patients. Maximal dialysate inflow volumes should be provided to enhance peritoneal kinetics.     

肾癌根治术患者手术前后CD8+CD28-T细胞表达及临床意义

【摘要】〓目的〓探讨肾癌根治术患者手术前后CD8+CD28-T细胞表达及临床意义。方法〓收集52例接受根治术的肾癌患者作为观察对象,采用流式细胞术检测手术前后外周血CD8+CD28-T细胞、白介素10(IL-10)及转化生长因子β1(TGF-β1)含量;分析三者含量与肿瘤分期的相关性,并以肾错构瘤患者及正常人作为对照。结果〓肾癌患者CD8+CD28-T细胞、IL-10及TGF-β1均显著高于另外两组,但肾错构瘤患者与正常人之间均无统计学差异(P<0.05);术前III期患者CD8+CD28-T细胞、IL-10及TGF-β1显著高于I及II期(P<0.05);术后各期肾癌患者CD8+CD28-T细胞及TGF-β1含量均显著低于术前(P<0.05),但IL-10却与术前无统计学差异;术后III期患者CD8+CD28-T细胞、IL-10及TGF-β1显著高于Ⅰ及Ⅱ期患者(P<0.05),但术前及术后I及II期患者上述三项指标均无统计学差异。相关性分析显示CD8+CD28-T细胞、IL-10及TGF-β1与分期均呈显著正相关性(P<0.05),其相关程度由大至小依次为CD8+CD28-T细胞>TGF-β1>IL-10。结论〓CD8+CD28-T细胞及其细胞因子表达含量增多可能是肾癌的一个新免疫机制,前者可在一定程度上鉴别肾癌与良性肿瘤,且可以评价手术效果。     

CD8+CD28-T细胞在脑疝患者的动态变化与临床意义

【摘要】 目的 探讨脑疝患者外周血CD8+CD28-T细胞的动态变化与临床意义。方法〓收集36例脑疝组(A组)患者外周血,以41例未出现脑疝的重型颅脑损伤患者(B组)及32例健康人(C组)作为对照,采用流式细胞术检测外周血CD8+CD28-T细胞及其胞内转化生长因子β1(TGF-β1)及白介素10(IL-10)百分含量。分别在伤后3 h、6 h及12 h观察A及B组患者外周血CD8+CD28-T细胞、TGF-β1及IL-10变化。结果〓三组CD8+CD28-T细胞、TGF-β1及IL-10总体差异均有显著性(P < 0.05),但B组与C组无统计学差异,而A组上述三者均显著低于另外B及C组(P < 0.05)。B组患者在伤后3 h、6 h及12 h的CD8+CD28-T细胞、TGF-β1及IL-10差异均无统计学意义|A组患者3 h、6 h及12 h的CD8+CD28-T细胞、TGF-β1及IL-10均呈进行性下降,表现为任意两个时间点的差异均有统计学意义(P < 0.05),且均显著低于B组(P < 0.05)。结论〓CD8+CD28-T细胞显著下降是脑疝患者的一个重要细胞免疫学特征,其伤后12h内进行性下降与病情进展密切相关。     

Expression of heat shock proteins 47 and 70 in the peritoneum of patients on continuous ambulatory peritoneal dialysis

BACKGROUND: Peritoneal sclerosis, characterized by collagen accumulation, is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis. METHODS: We determined the expression of HSP47 and HSP70 (nonspecific for collagen synthesis) by immunohistochemistry in peritoneal tissues of patients on CAPD. The tissue for collagen III, alpha-smooth muscle actin (alpha-SMA), and CD68 (a marker for macrophages) were also stained. Thirty-two peritoneal samples were divided into three groups (group A1, 11 patients who had no ultrafiltration loss; group A2, 9 patients who had ultrafiltration loss; and group B, 12 specimens who had end-stage renal disease prior to induction of CAPD. RESULTS: In group B, staining for HSP47, HSP70, and collagen III in peritoneal tissues was faint, and only a few cells were positive for alpha-SMA and CD68. In contrast, HSP47, HSP70, and collagen III were expressed in areas of thickened connective tissues in fibrotic peritoneal specimens of CAPD patients. The expression level of HSP47, HSP70, collagen III, and alpha-SMA and the number of CD68-positive cells in group A2 were significantly higher than those in groups A1 and B. HSP47/HSP70-positive cells were mesothelial cells, adipocytes, and alpha-SMA-positive myofibroblasts. Furthermore, the expression level of HSP47 was significantly higher in peritoneal specimens from patients with refractory peritonitis than without it and was significantly higher in patients with more than 60 months of CAPD therapy than that in patients with less than 60 months of CAPD. CONCLUSION: Our results indicate that CAPD therapy may induce HSPs in the peritoneal tissue, and that peritonitis in CAPD patients may be associated with the progression of peritoneal sclerosis at least through HSP47 expression and chronic macrophage infiltration. Our data also suggest that the progression of peritoneal sclerosis in such patients is associated with deterioration of peritoneal ultrafiltration function.     

Successive emergence of two CD 8 subsets in primary CMV infection of allograft recipients

Abstract Allograft recipients with cytomegalovirus (CMV) infection develop increased proportions of circulating CD8 lymphocytes. A longitudinal study of 11 kidney and 5 liver allograft recipients with primary CMV infection but no other aetiological factor to explain graft dysfunction revealed selective imbalances in peripheral blood CD8' T cell subsets. Initially, CMV viraemia was associated with elevated CD8+bright' T cell numbers and T cell activation. Activation markers fell to normal when viral cultures became negative (before the end of the 1st month). During the 2nd-6th months, most (12/16) patients continued to have high CD8⁺ T cell counts (1050–2900 CD8⁺ cells/mm3), comprising an uncommon CD8⁺ T cell subset, as 45–73% of CD8^{+ bright} lymphocytes were CD3⁺ and TCRαβ⁺ but were not stained by anti-CD28, CD11b, CD16, CD56 and CD57 antibody. Unexpectedly, CD 8⁺ CD 57⁺ T cells, a hallmark of CMV infection, did not appear until the 2nd-6th months of primary CMV infection, and their numbers increased progressively thereafter. They became the predominant CD8⁺ T cell subset after about 6 months of infection and their persistence for several (up to 4) years was strongly correlated ( r = 0.87) with expansion of CD8⁺ cells. Persistence of CD 8 lymphocytosis was, thus, directly related to the rate of expansion of an uncommon CD 8⁺CD 57^- subset and its progressive replacement by CD 8⁺CD 57 ⁺ T cells that were chronically elicited by CMV.     

Lymphocytes subsets in the course of continuous ambulatory peritoneal dialysis (CAPD)

BACKGROUND: We studied lymphocyte subset counts in comparison with normal subjects in order to clarify the abnormalities of cellular immune responses in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: The study included 37 CAPD patients and 45 normal individuals, as the control group. For the study, CAPD patients were divided into four groups depending on duration of replacement therapy. Group I consisted of patients treated for 0-6 months (n=6), group II for 6-12 months (n=6), group III for 13-24 months (n=16), and group IV for more than 25 months (n=9). Flow cytometry was used for estimation of lymphocyte subsets (determination of CD2, CD3, CD3+/CD4+, CD3+/CD8+, CD3-/16+56+, CD19, CD4/CD8). RESULTS: Our patients started CAPD with decreased lymphocyte subset counts, slightly above the normal range (excluding CD3 -/16+56+, CD2). After 6 months of CAPD therapy, an increase in CD4/CD8 ratio was observed and all examined lymphocyte subset counts decreased (excluding CD2). In patients on CAPD for more than 25 months, CD3+/CD4+, CD19 counts were below the normal range, CD3 -/16+56+ exceeded the upper limit of normal range and at the same time mean total lymphocyte count (TLC) was maintained in the normal range. CONCLUSIONS: We recommend lymphocyte subset determinations for detection of immune abnormalities in the course of CAPD treatment.     

CD4+ T cells, without CD8+ or B lymphocytes, can reject xenogeneic skin grafts

Abstract: Previous experiments have shown that rejection of xenogeneic skin grafts by mice is particularly dependent on CD4⁺ T cells. There are two possible explantations for this finding: either 1) "help" provided by CD4⁺ T cells is essential for CD8⁺ T cell-, B cell-, or NK cell-mediated effector mechanisms of rejection, or 2) CD4⁺ cells are themselves responsible for rejection, perhaps by some nonspecific effector mechanism. To examine these two hypotheses, we transplanted pig skin onto SCID mice and then reconstituted the mice with selected subpopulations of lymphocytes. Mice that did not received CD4⁺ T cells were unable to reject their xenografts, whereas those receiving CD4⁺ cells could do so in the absence of CD8⁺ cells or B cells and even when additionally depleted of NK cells by treatment with anti-Asialo GM1 antibody. Additional experiments were performed both in vivo and vitro to confirm the absence in test mice of CD4⁺ or CD8⁺ and B lymphocytes, respectively. These results suggest that CD4⁺ T cells are not only necessary for rejection of xenogeneic skin grafts by mice, but that they can do so without CD8⁺ cells or B cells, and probably without NK cells. Since CD4⁺ cells in mice have been shown to recognize xenogeneic antigens indirectly, this suggests that a nonspecific effector mechanism may be involved in the rejection of xenografts. In these experiments allogeneic skin grafts behave quite differently as they could not be rejected by this mechanism.     

Treatment of resistant CAPD peritonitis by temporary discontinuation of peritoneal dialysis

Resistant continuous ambulatory peritoneal dialysis (CAPD) peritonitis (recurrent or persistent infection) is traditionally treated by removal of the CAPD catheter and a period off peritoneal dialysis. In a pilot study we have treated 8 patients with recurrent staphylococcal peritonitis and 3 patients with persistent staphylococcal peritonitis by stopping CAPD for a 2-week period, the CAPD catheter being left in-situ. All 8 patients with recurrent peritonitis and 2 of the 3 patients with persistent peritonitis had resolution of their infection; the third patient required catheter removal to clear the infection. There were no acute problems associated with stopping CAPD, and there was no evidence of loss of peritoneal filtration capacity on restarting CAPD. This novel approach to the treatment of resistant CAPD peritonitis should reduce the number of CAPD catheters replaced and therefore diminish the risks and inconvenience to patients that such replacements entail.     

Functional CD25(bright+) alloresponsive T cells in fully immunosuppressed renal allograft recipients

BACKGROUND: Evidence from animal studies indicate a crucial role for CD25(bright+) regulatory T cells in transplantation tolerance. METHODS: To assess whether peripheral CD25(bright+) T cells control immune responses in immunosuppressed kidney transplant patients, we analyzed the suppressive capacities of these cells using mixed lymphocytes reactions. RESULTS: Allogeneic stimulation of patients peripheral blood mononuclear cells was associated with IL-2 production and T-cell proliferation. Depletion of CD25(bright+) T cells resulted in a 35% (median) higher IL-2 production and a 38% higher proliferative response against third party cells, showing that functional regulatory CD25(bright+) T cells were present (p = 0.03 and 0.02 respectively). In eight out of 11 patients, we also demonstrated regulation activity against donor-activated T cells (p = 0.03). These data were confirmed in coculture experiments with isolated CD25(-/dim) T cells plus CD25(bright+) T cells. At a 1:2 ratio, the CD25(bright+) T cells suppressed the proliferation of CD25(-/dim) donor- and third party-stimulated responder T cells. CONCLUSIONS: CD25(bright+) T cells with immune regulatory activities against anti-donor-responsive T cells are readily detectable in renal allograft recipients during treatment with full dosage immunosuppression. Whether CD25(bright+) T cells indeed play a role in graft acceptance after organ transplantation in patients remains to be elucidated.