心肺转流下室间隔缺损修补术患儿单个核细胞的变化

目的探讨室间隔缺损(VSD)患儿心肺转流(CPB)前后单个核细胞的变化。方法 CPB下行VSD修补术的患儿32例,分别于麻醉诱导后(T0)、停CPB即刻(T1)、术后第1天(T2)、第3天(T3)及第7天(T4)采集静脉血标本,应用流式细胞仪测定CD3+、CD4+、CD8+、CD19+、CD14+、CD16+CD56+细胞百分率;采用组织化学方法进行核仁组成区嗜银蛋白(AgNORs)染色并在全自动数码显微镜下测定其直径,计算每个细胞核中AgNORs的个数。结果与T0时比较,T1~T3时CD3+、CD4+均明显降低(P<0.05或P<0.01);T1时CD19+、CD14+明显降低(P<0.05或P<0.01),CD16+CD56+明显升高(P<0.01);T2时CD4+/CD8+明显降低(P<0.01),CD16+CD56+仍明显升高(P<0.01);T4时仅CD14+升高(P<0.05),其它指标均恢复到T0时水平。AgNORs形态类型为单一型,大都呈规则的圆形,CPB前后形态和数量无明显变化。结论单个核细胞的数量减少是细胞免疫功能受抑制的主要因素。     

Clinical significance of natural killer activity in patients with transitional cell carcinoma of the bladder

We studied the relationship of natural killer activity from peripheral blood mononuclear cells with clinical stage of disease and the different modalities of treatment in 67 untreated patients with transitional cell carcinoma of the bladder and 29 normal controls. Peripheral blood mononuclear cells from 39 patients with superficial bladder tumor (stages Ta and T1) showed a natural killer cell activity similar to that of controls (p greater than 0.05), while in 28 patients with infiltrating tumors (stages T2, T3 and T4) this activity was significantly depressed (p less than 0.01). This functional phenomenon cannot be ascribed to a deficient number of natural killer cells in patients with infiltrating tumors, since the amounts of HNK-1+ (Leu 7), CD16+ (Leu 11) and CD11b+ (OKM1) cells in peripheral blood mononuclear cells were similar in the 3 groups of subjects (p greater than 0.05). Furthermore, the natural killer activity of peripheral blood mononuclear cells was normal (p greater than 0.05) in patients who underwent transurethral resection of the tumors and intracavitary cytostatic therapy with doxorubicin who remained free of disease at least 6 months after treatment. However, in patients with superficial recurrent tumor a significant decrease in the natural killer activity of peripheral blood mononuclear cells was observed (p less than 0.05), which was more pronounced in those with infiltrating recurrence. Also, in the latter patients total cystoprostatectomy was associated with a relevant increase in the spontaneous level of peripheral blood mononuclear cells. We conclude that in patients with transitional cell carcinoma of the bladder there is a correlation of the levels of natural killer activity in peripheral blood mononuclear cells with clinical evolution and pathological stage of disease. The determination of this activity is useful to monitor patients with transitional cell carcinoma of the bladder.     

Characterization of lymphoid cells isolated from human gliomas

To analyze the phenotypic profile of lymphoid cells freshly isolated from surgically resected human gliomas, a double-immunostaining technique was developed which permitted the investigators simultaneously to distinguish between hematogenous and tumor cell populations and to detect expression of lymphocyte-monocyte subset-specific antigens on hematogenous cells. With this technique, the profiles of tumor-infiltrating lymphocytes (TIL's) derived from high- and low-grade gliomas were compared with phenotypes of lymphocytes concurrently isolated from peripheral blood. The total leukocyte cell yield from high-grade glioma cases exceeded that of low-grade cases. In nine high-grade glioma cases the proportion of CD8-positive cells was increased within the TIL population (41.2% +/- 1.9%, mean +/- standard error of the mean) as compared to the corresponding peripheral blood lymphocyte (PBL) population (30.8% +/- 4.1%, p less than 0.05). The proportion of natural killer HNK-positive cells, some of which bear the CD8 antigen (although not necessarily the pan T cell antigens CD2 and CD3), was also increased in the TIL's (41.9% +/- 4.2%) compared to that found in PBL's (32.1 +/- 5.6%, p less than 0.05) of high-grade glioma cases. The observed phenotypic pattern of high-grade glioma TIL's is similar to that reported based on immunohistochemical analysis of tumor tissue sections, suggesting that the techniques described here resulted in isolation of lymphoid cells representative of TIL's.     

Expression of cytolytic protein–perforin in peripheral blood lymphocytes in severe traumatic brain injured patients

PurposeThe purpose of this study was to investigate the changes of cytotoxic protein–perforin in peripheral blood lymphocytes in severe TBI patients and possible correlation between severity of TBI and perforin expression.MethodsFlow cytometry was used for simultaneous detection of intracellular perforin and cell surface antigens of peripheral blood lymphocytes of 20 severe TBI patients on day 1, 4 and 7 after the onset of injury. Peripheral blood mononuclear cells from 20 healthy volunteers were used as control. Clinical and laboratory parameters were also recorded.ResultsThere was a statistically significant decrease of perforin-positive lymphocytes including T, natural killer (NK) and NKT cells on day 4 as compared with day 1 after the brain injury or healthy controls. On day 7, perforin expression was restored in lymphocyte of cytotoxic phenotype (CD8⁺ T lymphocytes, NK cells, and NKT cells) compared with day 1. High positive correlation was found between the severity of TBI and frequency of perforin-positive cells on day 4 when the occurrence of the intra-hospital infections was the highest.ConclusionSevere TBI significantly decreases perforin expression in T lymphocytes, NK and NKT cells, which indicate a possible mechanism underlying the high susceptibility to infections.     

Patterns of human tumor-infiltrating lymphocytes in 120 human cancers.

Tumor-infiltrating lymphocytes from 120 samples of human cancers, including melanoma, renal cell carcinoma, breast cancer, sarcoma, and colon cancer, were examined. The percentage of lymphocytes recovered from the cancer varied widely; that of renal cell carcinoma was higher than that of breast or colon cancer (65% vs 45%), which was higher than that of melanomas or sarcomas (30% to 35%). The types of lymphocytes before and after interleukin 2 activation showed specific patterns. CD4+ helper T cells predominated in all tumors except melanomas, which had more CD8+ cytotoxic T cells. CD16+ natural killer cells were recovered in renal cell carcinoma and sarcomas. Three different cytotoxic lymphocytes were identified among interleukin 2-activated tumor-infiltrating lymphocytes: (1) CD3+ CD16- cytotoxic T lymphocytes with cytotoxicity restricted to autologous tumor cells in melanomas, (2) CD3-CD16+ natural killer cells with vigorous major histocompatibility complex-nonrestricted cytotoxicity in renal cell carcinoma, and (3) CD3+ CD16- T cells with modest levels of major histocompatibility complex-nonstricted cytotoxicity in all cancers except melanomas. Thus, there was considerable diversity of tumor-infiltrating lymphocytes among these histologically distinct tumors with respect to magnitude of lymphocyte infiltration, phenotypic expression, and functional capacity.     

体外循环心内直视手术对患者外周血白细胞中性粒细胞T淋巴细胞亚群影响

选择３０例择期心内直视术患者，治疗期间连续观察麻醉前后、术毕、术后第１、７、１４天其外周血白细胞、中性粒细胞、Ｔ淋巴细胞亚群变化，借以判断麻醉与体外转流手术后上述免疫参数变化，为及时防治心内直视术患者术后并发症提供实验依据。结果发现静吸复合麻醉近１ｈ后外周血淋巴细胞数急剧下降，术毕、术后第１至１４天外周血白细胞、中性粒细胞数及其所占百分率显著升高，而淋巴细胞数及其百分率则明显下降。Ｔ淋巴细胞亚群分析发现麻醉后ＣＤ＋３、ＣＤ＋４细胞及ＣＤ＋４／ＣＤ＋８比值明显下降，术毕、术后第１天进一步下降，至术后第７天或１４天恢复至麻醉前水平，这些参数变化是患者术后易并发感染等的原因之一。     

Warm ischemia induces alteration in lung immune cell functions

Warm ischemia is an important factor in early allograft dysfunction. To elucidate cellular events involved in such lung injury, we examined the effects of warm ischemia on the cytotoxic function of lymphocytes retrieved by bronchoalveolar lavage as compared with peripheral blood lymphocytes. Warm ischemia of the lung was induced in eight dogs by crossclamping left hilar structures for 1 hour. Bronchoalveolar cells from ischemia left and unaffected right lungs, as well as blood lymphocytes, were isolated before operation and 2 hours, 72 hours, and 7 days after operation. Lung and blood lymphocytes were assayed for natural killer and lectin-dependent cell-mediated cytotoxicity. Warm ischemia resulted in a significant impairment of natural killer activity within 2 hours of reperfusion (49% of preoperative control cytolysis, p less than 0.01). There was a significant increase in natural killer activity in bronchoalveolar lavage mononuclear cells 72 hours after reperfusion injury (178.4% of preoperative value, p less than 0.01). Interestingly, these functional alterations were not paralleled with changes seen in the peripheral blood lymphocytes or the opposite nonaffected lungs, where the natural killer activity appeared significantly depressed at 72 hours. Similarly, lectin-dependent cell-mediated cytotoxicity was noted to be increased in the bronchoalveolar lavage from the ischemic lung (179.5%, p less than 0.01) but decreased in the bronchoalveolar lavage from the nonaffected lung and peripheral blood lymphocytes at 72 hours after injury. We conclude that warm ischemia is associated with a functional alteration of the local lung immune cells. Such alteration is not observed in cells from the opposite lung or peripheral blood. The observed increase in nonspecific cytotoxicity of bronchoalveolar lymphocytes can be causative in the early damage seen in poorly preserved lung allografts.     

Natural killer cell and alphabeta and gammadelta lymphocyte traffic into the liver graft immediately after liver transplantation

BACKGROUND: The persistence and migration of donor leukocytes has been well established, but cellular kinetics immediately after revascularization and the potential relevance of these different lymphocyte populations to spontaneous tolerance remain unclear. During the early hours of revascularization, there is a transitory "congestion" of the liver graft, which is evidence of an early phase that we have termed "first cellular contact." METHODS: We have carried out by flow cytometry a prospective comparative study of the peak kinetics of lymphocyte subpopulations contained in: (a) peripheral blood and liver grafts at the time of multi-organ extraction from 14 brain-dead donors, (b) recipient peripheral blood before transplantation, and (c) recipient peripheral blood and liver grafts after (t=2 h) declamping and vascularization of the liver graft. RESULTS: Before transplantation, the liver grafts contained large numbers of natural killer (NK) and NK-like cells with early lymphocyte activation. Immediately after revascularization, there was an influx of recipient NK and NK-like cells into the liver. CONCLUSIONS: NK and CD3+CD56+ (NK-like) cells flooding into the liver graft immediately after revascularization could rapidly destroy allogeneic cells. However, spontaneous tolerance and the persistence of donor lymphocytes after orthotopic liver transplant could be a result of donor TCRalphabeta NK1.1 liver graft lymphocytes, which may be involved in the destruction of CD8+ T lymphocytes that would have received the apoptosis signal, and to NK and NK-like cell inhibition via inhibitory NK receptors. The decrease in gammadelta T lymphocytes in the two compartments suggests a mechanism of recirculation and capture in other lymphoid organs.     

Mesenteric complications after hypothermic cardiopulmonary bypass with cardiac arrest: underlying mechanisms

The aim of this study was to determine the pathophysiological mechanisms of postcardiopulmonary bypass (CPB) intestinal dysfunction using an in vivo canine model of extracorporeal circulation. Six dogs underwent a 90 min hypothermic CPB with continuous monitoring of mean arterial blood pressure (MAP) and mesenteric blood flow (MBF). Reactive hyperemia and vasodilator responses of the superior mesenteric artery to acetylcholine and sodium nitroprusside were determined before and after CPB. Mesenteric lactate production, glucose consumption, creatine kinase (CK) release and venous free radicals were determined. CPB induced a significant fall (p < 0.05) in MAP and MBF. After CPB, reactive hyperemia (-26 +/- 15% versus -53 +/- 2%, p < 0.05) and the response to acetylcholine (-42 +/- 9 versus -55 +/- 6%, p < 0.05) were significantly decreased. Reperfusion increased lactate production (0.8 +/- 0.09 mmol/L versus 0.4 +/- 0.18, p < 0.05) and the CK release (446 +/- 98 U/L versus 5 +/- 19 U/L, p < 0.01). Endothelial dysfunction, conversion from aerobic to anaerobic metabolism, and intestinal cell necrosis seem to be responsible for intestinal complications associated with CPB.     

Altered cellular immune function in the atelectatic lung

Pulmonary atelectasis is common and may predispose the lung to infection. We have previously shown that atelectasis impairs alveolar macrophage antibacterial function. This study examines the effect of atelectasis on the cytotoxic function of lymphocytes harvested from the bronchoalveolar space of atelectatic lung segments by bronchoalveolar lavage. Specifically, we studied natural killer and lectin-dependent cell-mediated cytotoxicity in peripheral blood and bronchoalveolar lavage lymphocytes from the atelectatic lower lobes and contralateral normal lobes in a group of 8 dogs. We observed a decline of natural killer and lectin-dependent cell-mediated cytotoxicity to 62.7% and 61.5%, respectively, of preatelectasis control values in the affected lung lobes (p less than 0.01). Simultaneous measurements of cytotoxic activity of bronchoalveolar lavage lymphocytes harvested from the unaffected contralateral normal lungs were comparable with control values. On the other hand, natural killer and lectin-dependent cell-mediated cytotoxicity activities in peripheral blood lymphocytes were significantly increased in animals having right lower lobe atelectasis (166.7% and 154.7% of pretreated normal control, respectively, p less than 0.01). Atelectasis was also associated with an influx of polymorphonuclear leukocytes into the bronchoalveolar compartment. These findings confirm the presence of natural killer cells and cytotoxic lymphocytes in the bronchoalveolar compartment and demonstrate an atelectasis-induced impairment of local bronchoalveolar lymphocyte function. Such a dysfunction of local lung cellular host defenses may render the atelectatic lung susceptible to infection.     

Minimally invasive versus open Roux-en-Y gastric bypass: effect on immune effector cells

BackgroundMinimally invasive surgery (MIS) has several potential benefits compared with the open approach, including potentially less perioperative immunosuppression. Data characterizing the differential stress responses have been limited to serum cytokine analyses and animal studies. We hypothesized that the open approach to Roux-en-Y gastric bypass (RYGB) has a more deleterious, negative, quantifiable effect on the peripheral blood mononuclear cells than does the MIS approach.MethodsPatients undergoing open and MIS RYGB for morbid obesity had blood samples collected preoperatively and postoperatively on days 1 and 2 and at the first follow-up visit. The peripheral blood mononuclear cells were isolated and analyzed for phenotype using flow cytometry, natural killer cell cytotoxicity using 51-chromium release assay, and gene expression using Affymetrix U133 Plus 2.0 microarray.ResultsPatient age and body mass index were similar between the 2 groups. Postoperatively, differences within the open group were seen for CD3+/CD16? (T lymphocytes), CD3?/CD16+ (natural killer cells), CD3+/CD4+ (T-helper lymphocytes), and CD4/CD8 subsets (P <.05). No differences were seen within the open group CD3+/CD8+ (cytotoxic T lymphocytes) or within the MIS subsets. Between the 2 approaches, no phenotypic differences were found, except for the postoperative day 1 CD3+/CD16? (P <.05). Within each group, significant decreases were found in cytotoxicity on days 1 and 2 compared with preoperatively (P <.05). The cytotoxicity seen after MIS had returned to the preoperative levels at the first follow-up visit, but the cytotoxicity after open RYGB had not (P <.05). Between the 2 groups, the open group had greater cytotoxic decreases than did the MIS group at postoperative days 1 and 2 (P <.05). Microarray analysis of the preoperative (n = 20) and day 2 (n = 20) specimens identified a 20-gene signature that correlated with the surgical approach.ConclusionOpen RYGB surgery causes greater inhibition of innate immunity than does MIS. This inhibition was not accounted for by phenotypic changes. Gene expression changes from surgical stress might represent the molecular basis of this differential immune response.     

Variation of bronchoalveolar lymphocyte phenotypes with age in the physiologically normal human lung

BACKGROUND: Changes in T lymphocyte subsets have been observed in various forms of pulmonary disease. However, bronchoalveolar lymphocyte subsets have not been well characterised for healthy individuals differing in age. A study was undertaken to investigate the bronchoalveolar lavage (BAL) and peripheral blood lymphocyte subsets in clinically normal volunteers of two different age groups (19-36 and 64-83 years). METHODS: Bronchoalveolar lavage was performed on all individuals in both age groups and peripheral venous blood was drawn just prior to BAL. Bronchoalveolar cell profiles were characterised by morphological criteria, and cell surface antigen expression of lymphocytes was determined by flow cytometry. RESULTS: A significant increase in total BAL lymphocytes was observed for the oldest group compared with the youngest age group. Mean lymphocyte subset (CD4+/CD8+) ratios were significantly increased in BAL fluid from the older group compared with the younger group (mean (SE) 7.6 (1.5) vs 1.9 (0.2); p<0.0001). The increase in the BAL CD4+/CD8+ T cell ratio was mostly due to an increase in relative numbers of CD4+ lymphocytes, and the BAL CD4/CD8 ratio was disproportionately increased compared with peripheral blood in the older group. Increased expression of HLA-DR and CD69 on CD4+ T lymphocytes was observed in the oldest age group. Relative numbers of natural killer (NK) cells did not vary with age, and gammadelta T cells and CD5+ B cells were present in very low numbers in both age groups. CONCLUSIONS: CD4+ T cells accumulate in air spaces of the lower respiratory tract with age in healthy adults and express increased amounts of HLA-DR and CD69 on their surfaces, suggesting a relative degree of CD4+ T lymphocyte activation for healthy older individuals who have normal lung function.     

Immunocytochemical Analysis of Cellular Infiltrates in Human Appendicitis

This study was conducted to determine the immunologic cellular composition in human ap-pendicitis and its association with the development of perforated appendicitis. Appendiceal specimens from 27 patients with acute appendicitis were immunostained to detect lymphocyte surface markers. Moreover, the lymphocyte surface markers of peripheral blood were analyzed by laser flow cytometry in 12 patients. Helper T lymphocytes (CD4) were present in all the patients, while B lymphocytes (CD19), natural killer (NK) cells (CD56), and cytotoxic T lymphocytes (CD8) were present in 7 (70%), 10 (100%), and 9 patients (90%) with perforated appendicitis, and in 12 (63.2%), 10 (58.8%), and 6 (54.5%) patients without perforation, respectively. There were significant differences between the patients with a perforated appendix and those without perforation, in the positivity rate for CD8 and CD56 cells (P < 0.05). The number of cells positive for CD56, being NK cells, in the blood from the patients with perforation was significantly lower than that in the blood from those without perforation (P < 0.05). The infiltration of a greater number of cytotoxic T lymphocytes and NK cells was observed in the appendices from patients with perforated appendicitis than in those from patients with nonperforated appendicitis. Received: December 8, 1999 / Accepted: July 25, 2000     

Immunopathology of early graft-versus-host disease--a prospective study of skin, rectum, and peripheral blood in allogeneic and autologous bone marrow transplant recipients.

The immunopathological appearances of skin and rectum in 64 autologous and allogeneic recipients were determined before and after bone marrow transplantation. Patients who developed acute graft-versus-host disease were biopsied as soon as a clinical diagnosis was made. At the same time peripheral blood samples were collected for comparative analysis. Immunohistological and morphometric techniques were employed using a panel of monoclonal antibodies to T lymphocytes and subsets, B lymphocytes, natural killer cells, macrophages, and Langerhans cells. A reduction in the CD4/CD8 ratio after BMT was seen in skin and rectal biopsies from both autologous and allogeneic recipients with or without GVHD. The same pattern was observed in blood samples taken at the same time. Langerhans cells were reduced in the skin in all patients after BMT, probably by the conditioning regimen. Only a few cells expressing activation or natural killer cell markers were present and there were no changes observed in the macrophage population. This study has provided no evidence to implicate either CD4- or CD8-positive T lymphocytes as the initiators of the cellular damage in acute GVHD. The distribution of lymphocyte subsets in the blood was similar to that in the tissues, suggesting that the tissue changes reflect the pattern of lymphocyte repopulation after BMT and may have little bearing on the pathogenesis of GVHD.     

Specific cytotoxic activity of T lymphocyte clones derived from a patient with gliosarcoma

Eleven lymphocyte clones were established from the peripheral blood lymphocytes of a patient with gliosarcoma by means of autologous tumor stimulation and the limiting-dilution technique with recombinant interleukin-2. Ten of the 11 clones were cytotoxic against the autologous tumor cell line GI-1. Seven of the 10 clones were also cytotoxic against allogeneic brain-tumor lines and HeLa cells, one clone was cytotoxic against several target cells, and two clones were specifically cytotoxic against GI-1 and allogeneic brain-tumor cells. One of the 11 clones was not cytotoxic against any target cells tested. Lymphokine-activated killer cells induced by recombinant interleukin-2 alone exhibited cytotoxic activity against all target tumor cells tested. Surface phenotypic analysis revealed that all lymphocyte clones expressed CD3 antigen, some expressed CD4 antigen, and others expressed CD8 antigen. These clones seemed to be antigen-specific cytotoxic T lymphocyte clones. Analysis with these antigen-specific cytotoxic T lymphocyte clones may be useful in the elucidation of tumor-specific or tumor-associated antigens on autologous tumor cells.     

ESWL和输尿管镜下气压弹道碎石术对输尿管结石患者T细胞亚群和NK细胞的影响

目的:探讨体外冲击波碎石术(ESWL)和输尿管镜下气压弹道碎石术(URS-PL)对输尿管下端结石患者T细胞亚群和自然杀伤细胞(NK细胞)的影响及临床意义。方法:收集本院输尿管下段结石61例,行体外冲击波碎石术31例(ESWL组),行输尿管镜下气压弹道碎石术30例(URS-PL组),两组患者分别于术前1天、术毕30 min、术后1天以及术后4天抽取肘静脉血,通过流式细胞仪检测T细胞亚群和NK细胞。统计并比较分析两组患者T细胞亚群、T细胞增殖活性、NK细胞含量以及杀伤活性。结果:ESWL组术后CD_3~+、CD_4~+ T细胞比例、CD_4/CD_8比值、NK细胞比例和杀伤活性无明显变化;URS-PL组术后1天CD_3~+、CD_4~+T细胞比例、CD_4/CD_8比值、NK细胞比例和杀伤活性明显下降(P0.05),与ESWL组比较差异有统计学意义(P0.05),术后4天恢复正常。ESWL组与URS-PL组患者围手术期T细胞增殖变化比较差异无统计学意义(P0.05)。结论:治疗输尿管下段结石,体外冲击波碎石术相对输尿管镜下气压弹道碎石术对T细胞亚群和NK细胞的抑制更细微。免疫应答反应作为监测机体创伤程度这一因素将对选择ESWL和URS-PL治疗输尿管下段结石具有临床指导价值。     

In vitro study of expression of interleukin-2 receptors in T-lymphocytes from patients with IgA nephropathy

The present study was undertaken to examine the expression of interleukin-2 receptor (IL-2R)/CD25 antigen in cultured T-lymphocyte subsets in IgA nephropathy. Twenty-four IgA nephritic patients, 12 patients with chronic glomerulonephritis (non-IgA nephropathy), and 17 healthy controls were studied in an infection-free interval. T-cell subsets in peripheral blood mononuclear cells (PBMC) and activated T-lymphocyte subsets expressing IL-2R were determined by double immunofluorescence staining with fluorochromes conjugated to monoclonal antibodies against T-helper/inducer (CD4+) cell, T-suppressor/cytotoxic (CD8+) cell, B (CD20+) lymphocytes, and IL-2R. The percentages of CD4+ and CD8+ lymphocytes, CD4/CD8 ratio, and total activated lymphocytes (with IL-2R/CD25 antigen) did not differ between the IgA nephritic patients, patients with chronic glomerulonephritis, and healthy controls in freshly isolated, unstimulated lymphocytes or PBMC cultured with pokeweed mitogen. Following pokeweed mitogen stimulation for 5 days, 17.3 +/- 10.3%, 16.6 +/- 8.4%, and 16.7 +/- 9.4% of PBMC from IgA nephritic patients, patients with chronic glomerulonephritis, and controls respectively expressed IL-2R (p greater than 0.05). However, the individual T-cell subsets bearing IL-2R were distinctly different between the IgA nephritic patients and patients with chronic glomerulonephritis or healthy controls. IgA nephritic patients had increased activated CD4+ lymphocytes (with IL-2R) (p less than 0.025) and reduced activated CD8+ lymphocytes (p less than 0.025). Our study suggests a defective immunoregulation in IgA nephropathy with enhanced T-helper/inducer and reduced T-suppressor/cytotoxic activity when stimulated with mitogen and probably, during clinical exacerbation.     

Lymphocyte subsets in renal allograft recipients with chronic hepatitis C virus infection.

BACKGROUND: The pathogenetic mechanisms of chronic hepatitis C virus (HCV) infection in renal allograft recipients are not well established. This study aimed to examine the relationship between altered immune status and HCV-related liver disease, by determining the changes in peripheral blood lymphocyte and natural killer (NK) cell subsets in these subjects. METHODS: Peripheral blood lymphocyte, NK cell and activation markers were detected by flow cytometry in renal allograft recipients with (TpC+) or without (TpC-) HCV infection, and compared with age- and sex-matched patients with post-transfusional chronic HCV infection (TfC+) and healthy controls. RESULTS: CD19+ cells were reduced in renal allograft recipients compared with controls. TpC+ subjects had increased CD3+CD8+ cells compared with controls, and increased CD3+DR+ cells but reduced CD4+ CD38+ and CD3-CD16/56+ cells compared with controls as well as TfC+ patients. TfC+ patients and controls had similar numbers and proportions for the lymphocyte subsets and NK cells. Chronic liver disease in HCV-infected renal allograft recipients was associated with increased CD3+CD16/56+ cells but reduced CD4+CD38+ cells. Reduction of CD3-CD16/56+ cells was noted in TpC+ subjects without liver disease. Yet among post-transfusional (TfC+) subjects this was associated with chronic hepatitis. CONCLUSIONS: Peripheral blood suppressor/cytotoxic T lymphocytes are increased, whereas activated helper/inducer T lymphocytes and NK cells are reduced, in renal allograft recipients with HCV infection. Increased non-MHC-restricted cytotoxic T cells and reduced NK cells are associated with the presence or absence of liver disease respectively. These data suggest that immune mechanisms are important in the pathogenesis of chronic hepatitis C after renal transplantation.     

The characterization of peritoneal and pleural exudate cells from malignant effusions

The immune function of peripheral blood cells and cells from the pleural and abdominal effusions of patients with advanced cancer was compared to that of peripheral blood cells from controls. The parameters examined included lymphocyte subsets, natural killer (NK) cell activity, and anti-Daudi and lymphokine-activated killer (LAK) cell activity. The percentage of CD4⁺ pleural and peritoneal exudate cells (PEC) was significantly higher than the percentage of peripheral blood mononuclear cells (PBMC) in the patients. The percentage of CD8⁺CD11⁺ PEC and PBMC, being the suppressor T-cells, of the patients was increased compared with controls, while the percentage of CD8⁺CD11^– PEC, being the cytotoxic T-cells, was identical to the PBMC of both patients and controls. The NK activity of PEC was significantly lower than that of PBMC in both patients and controls, and there was no correlation between the NK activity of PBMC and PEC. Although the anti-Daudi activity of PEC was markedly low, LAK cells with high activity could be induced by culture with interleukin-2 for 4 days. These results suggest that the immune function of cells in malignant effusions may be depressed due to a low population of cytotoxic T cells, low NK activity and increased suppressor T cells, while the local administration of interleukin-2 may induce LAK cells. Therefore, effective local immunotherapy for malignant effusions should not only augment effector cells, but also inhibit supprssor cells.     

The prognostic value of peripheral blood lymphocyte subsets in patients with bladder carcinoma treated using neoadjuvant M-VEC chemotherapy

OBJECTIVES: To assess the prognostic value of peripheral blood lymphocyte subsets in patients with bladder cancer who were treated with neoadjuvant chemotherapy. PATIENTS, SUBJECTS AND METHODS: Thirty patients with a histological diagnosis of invasive bladder transitional cell carcinoma and 30 age-matched controls with no evidence of cancer and immunological disorders were evaluated. Peripheral blood samples were assessed in both groups using monoclonal antibodies. Patients with bladder cancer who achieved complete or partial responses and those who had progression of the disease after systemic chemotherapy with methotrexate, vinblastine, epirubicin and cisplatin were compared according to the pretreatment values of the peripheral blood lymphocyte subsets. RESULTS: There were no significant differences in B lymphocyte levels between the groups. In patients with bladder cancer, the percentages of T lymphocytes (P<0.01), natural killer (NK) cells (P<0.05) and the CD4+/CD8+ ratio (P<0.05) were significantly lower than in the control group. In patients who responded to the chemotherapy regimen, the pretreatment values of T lymphocytes (P<0.001), the CD4+/CD8+ ratio (P<0.01) and NK cell levels (P<0.01) were significantly higher than in the patients who did not. CONCLUSION: In patients with invasive bladder carcinoma, cell-mediated immunity may have a role in the resistance to this malignancy and in these patients the pretreatment levels of T lymphocyte subsets may be an indicator of the potential response to chemotherapy.