化疗在中晚期非小细胞肺癌患者中对淋巴细胞亚群影响分析

目的:探讨化疗在中晚期非小细胞肺癌患者中对淋巴细胞亚群的影响。方法:随机抽取本院收治的60例中晚期非小细胞肺癌患者编为实验组进行化疗,另选取同期体检的50例健康志愿者作为对照组。随访12月-15月,采用流式细胞仪技术分别对两组外周血淋巴细胞亚群进行检测计数。结果:两组间相比,实验组患者的CD3+、CD4+、NK细胞的数量以及CD4+/CD8+比值均低于对照组(P<0.05),而CD8+细胞的比例却高于对照组。化疗后CD3+、CD4+、CD4+/CD8+、NK均较化疗前升高(P<0.05),但CD8+不变(P>0.05)。结论:应用化疗治疗中晚期非小细胞肺癌,可明显改善患者的免疫功能。     

Use of mildronate in therapy of seroresistant syphilis (serologic and immunologic comparisons

Clinico-serological and immunological examinations were applied to 84 patients suffering from seroresistant syphilis with positive serological reactions within 1.5 to 10 years after termination of the treatment by various methods. The initial diagnosis of recently inflicted secondary syphilis was recorded in 8.9 per cent of the patients. 43.3 and 47.8 per cent of the patients had secondary relapsing syphilis and early occult syphilis, respectively. The percentage of lymphocytes CD3+, CD4+, CD8+ and HLA DR+ was determined in peripheric blood with the monoclonal antibodies OKT-3+, OKT-4+, OKT-8+ and FITC-labeled antimouse Ig. The quantity of IgA, IgG and IgM was determined by radial immunodiffusion. The immunoregulatory index (IRI, the ratio of T-helper/inductor cells and T-suppressor cells/cytotoxics) was calculated. The use of mildronate, a drug developed at the Institute of Organic Chemistry of the Academy of Sciences of the Latvian SSR (Riga), led to normalization of the impaired immunological indices and complete negativation of the serological reactions in the group of the patients with disorders in the immunity status (CD8+ - 33 per cent and IRI - 1.3), p less than 0.01.     

曲马多、吗啡术后自控镇痛对食管癌患者细胞免疫功能的影响

目的：比较曲马多、吗啡对食管癌术后患者的镇痛疗效以及对机体免疫功能的影响。方法：将本院50 例行食管癌手术患者随 机分成对A 组和B 组,A 组接受硬膜外吗啡镇痛,B 组接受硬膜外曲马多镇痛,常规监测心电图（ECG）、无创血压（BP）、心率 （HR）、血氧饱和度（SPO2）、呼气末二氧化碳分压(PETCO2）。记录两组患者不同时间点视觉模拟疼痛（VAS）评分、不良反应发生 率、外周血T 淋巴细胞亚群(CD3+、CD4+、CD8+)、NK 细胞的变化。结果：两组患者均得到满意的术后镇痛效果,术后1d,A、B两组 患者外周血T淋巴细胞亚群、NK 细胞的水平较术前降低（P<0.05）,且A 组降低幅度明显大于B 组（P<0.05）;术后2d,A 组外周 血T 淋巴细胞亚群、NK 细胞的水平虽有所升高,但仍较术前降低（P<0.05）,B 组CD3+、CD4+、CD8+及NK细胞水平恢复至术前水 平;术后3d,A 组上述指标恢复至麻醉前水平。结论：曲马多在镇痛的同时对机体外周血T 淋巴细胞亚群和NK细胞水平影响较 小,减轻了麻醉对细胞免疫功能的抑制效应。     

Liver CD4-CD8- NK1.1+ TCR alpha beta intermediate cells increase during experimental malaria infection and are able to exhibit inhibitory activity against the parasite liver stage in vitro

Experimental infection of C57BL/6 mice by Plasmodium yoelii sporozoites induced an increase of CD4-CD8- NK1.1+ TCR alpha beta int cells and a down-regulation of CD4+ NK1.1+ TCR alpha beta int cells in the liver during the acute phase of the infection. These cells showed an activated CD69+, CD122+, CD44high, and CD62Lhigh surface phenotype. Analysis of the expressed TCRV beta segment repertoire revealed that most of the expanded CD4-CD8- (double-negative) T cells presented a skewed TCRV beta repertoire and preferentially used V beta 2 and V beta 7 rather than V beta 8. To get an insight into the function of expanded NK1.1+ T cells, experiments were designed in vitro to study their activity against P. yoelii liver stage development. P. yoelii-primed CD3+ NK1.1+ intrahepatic lymphocytes inhibited parasite growth within the hepatocyte. The antiplasmodial effector function of the parasite-induced NK1.1+ liver T cells was almost totally reversed with an anti-CD3 Ab. Moreover, IFN-gamma was in part involved in this antiparasite activity. These results suggest that up-regulation of CD4-CD8- NK1.1+ alpha beta T cells and down-regulation of CD4+ NK1.1+ TCR alpha beta int cells may contribute to the early immune response induced by the Plasmodium during the prime infection.     

Natural killer cells in patients with pulmonary tuberculosis]

In the existent literature the number of works devoted to the subpopulation of natural killer cells (NK) is not significant. The purpose of the present study was to determine the NK content in the blood of pulmonary tuberculosis patients; to establish correlation of the level of their content with the content of the previously studied T-lymphocyte subpopulations; to determine the intensity of the fluorescence of NK, CD3+, CD4+, CD8+ lymphocytes. The data were obtained on the significant increase in the NK mean level in tuberculosis patients (20.37 +/- 1.74) as compared with that in healthy subjects (12.77 +/- 2.56). The NK fluorescence intensity (56.33 +/- 2.28) conditioned by the Fc-receptor expression intensity is significantly lower than the analogous index in healthy volunteers (82.4 +/- 7.69). The NK level in the blood of tuberculosis patients correlates with the content of CD3+, CD8+ lymphocytes as well as with the CD4+/CD8+ index.     

The clinical value of the changes of peripheral lymphocyte subsets absolute counts in patients with non-small cell lung cancer

IntroductionImmune function strongly influences the outcome of patients with non-small cell lung cancer (NSCLC). It's vital to understand the immune state of patients through detecting the percentage and number of lymphocyte subsets accurately, and helpful to evaluate conditions of prognosis and adjust treatment for patients.MethodsWe conducted a retrospective cohort study in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. The absolute counts and percentages of CD3+, CD3 + CD4+, CD3 + CD8+, B and NK cells were determined by single platform technologies. 172 patients received treatment including surgery or chemotherapy after surgery. The factors affecting disease progression were analyzed by Binary Logistic regression. Progression free survival (PFS) calculating survivals were with the method of Kaplan-Meier. The log-rank test and cox's proportional hazard regression (enter method) were used for univariable and multivariable analyses respectively.ResultsRelative to normal controls, patients with NSCLC at different stages showed decreased absolute lymphocyte count obviously, rather than lymphocyte percentages.Different treatments had unlike influence on the homeostasis of lymphocytes and the effects last for a long time. Logistic regression showed CD3 + CD4+ and CD3 + CD8+ could contribute to favorable prognosis. Multivariate analysis of prognostic factors of PFS showed CD3 + CD4+ cell was independent factor for predicting PFS.ConclusionsThe absolute count of CD3+, CD3 + CD4+, CD3 + CD8+, B and NK cells were better indication of the patient's immune state than percentages of each lymphocyte subsets. Immune function was impaired in patients with non-small cell lung. The high level of baseline absolute CD3 + CD4+ cells count contributed to longer progression free survival.Chinese Clinic Trial Registry number: ChiCTR-IOR-17014139; Registry date: 2017/12/25.     

Immunologic and clinical aspects of natural killer cells in human leukemia

We have studied peripheral-blood, splenic and bone marrow natural killer (NK) activity in patients with leukemia. These studies demonstrated that leukemic patients displayed defective NK activity in all of these tissues. However, NK defect could be corrected by culture of effector cells with interleukin-2 (IL-2). The phenotypic analysis of IL-2 cultures showed clearly the heterogeneity of lymphocyte subsets. The characterization studies demonstrated that CD56+, CD3- NK cells manifested most potent lysis of leukemia, CD56+, CD3+ T cells mediated some, but low, antileukemia activity and CD56-, CD3+ T lymphocytes were devoid of cytotoxicity.     

Immunologic monitoring studies in advanced cancer patients treated with recombinant human gamma interferon (IFN-gamma 4A)

Thirty-nine patients with a variety of advanced malignancies were treated with recombinant IFN-gamma 4A (AMGen, specific activity 1 to 5 x 10(7) U/mg protein). IFN-gamma 4A was administered at a dose of 10-2,000 micrograms/m2/d. Following a 2-week rest, a maintenance phase was continued with injections 3 d/wk. Immunologic monitoring studies were performed on patients' peripheral blood cells before administration of IFN-gamma 4A, then on Days 15 and 90. Flow cytometric analysis was used to determine the absolute number of CD 3+, CD 4+, CD 8+, CD 19+, and CD 16+ cells using a panel of monoclonal antibodies. Natural killer (NK) cell function was assayed by monitoring lysis of the K562 cell line in the Cr51 release assay. Changes from baseline were observed on Days 15 and 90 in all parameters studied, although the ratio of helper to suppressor cells seemed to remain within the normal range. Whereas there were no substantial changes in CD 3+ and CD 4+ cells on Day 15, IFN-gamma 4A had an enhancing effect on CD 8+, CD 19+, and CD 16+ cells. This trend continued at Day 90 only for CD 19+ and CD 16+ cells at the higher dose levels. An increase in functional NK cell activity at Day 15 was less noted on Day 90. Comparison of intravenous (IV) to intramuscular-subcutaneous (IM-SC) administration showed differences in the effect on lymphocyte subpopulations at 450 and 1,000 micrograms. The effect of IFN-gamma 4A on the equilibrium among lymphocyte subpopulations and the possibility of its role in combination therapy with other biologic response modifiers are discussed.     

阿莫西林联合甲强龙治疗老年支气管肺炎患者的临床效果及机制分析

目的：探讨阿莫西林联合甲强龙治疗老年支气管肺炎患者的临床效果及其可能的作用机制。方法：选取我院呼吸科收治的 老年支气管肺炎患者84例,根据治疗方案不同分为常规组及试验组。比较两组患者治疗前后临床体征、IgA、IgM、IgG、CD4+及 CD8+T 淋巴细胞、NK 细胞及血清LDH3、LDH4、HBDH水平的变化情况。结果：治疗后,试验组咳喘、高热、肺内干湿罗音的恢复 时间明显短于常规组,IgA、IgM、IgG、LDH、HBDH、NK 细胞及CD8+T 淋巴细胞水平明显低于常规组,CD4+T 淋巴细胞水平明显 高于常规组,差异均具有统计学意义(P<0.05)。结论：阿莫西林联合甲强龙可有效快速改善老年支气管肺炎患者的临床症状,这可 能与其降低IgA、IgM、IgG、LDH、HBDHNK 细胞及CD8+T 淋巴细胞水平及提高CD4+T 淋巴细胞水平有关。     

地佐辛对妇科恶性肿瘤患者术后镇痛疗效及免疫功能的影响

目的:探究地佐辛在妇科恶性肿瘤术后镇痛中的疗效及对其围手术期免疫功能的影响,为临床手术用药提供依据。方法:选择2012年7月~2015年9月期间我院行妇科恶性肿瘤手术患者87例为研究对象,采用随机数字法将其分为地佐辛组(45例)和对照组(42例),地佐辛组患者给予全身麻醉联合地佐辛治疗,对照组患者给予全身麻醉联合芬太尼治疗,记录并分析两组患者术中、术后VAS疼痛评分、Ramsay镇静评分及免疫指标。结果:两组患者术后各时间点的VAS评分均分均小于4分,地佐辛组患者在T3时刻VAS评分显著低于对照组(P0.05);与T1时刻比较,T2、T4时刻地佐辛组患者CD3~+、CD4~+、CD4~+/CD8~+及NK细胞水平均显著降低(P0.05),T2时刻地佐辛组患者CD8~+水平显著升高(P0.05);对照组T2时刻CD3~+、CD4~+、CD4~+/CD8~+及NK细胞水平,T4时刻CD3~+、NK细胞水平,T5时刻NK细胞水平均出现明显降低(P0.05);地佐辛组患者T5时刻CD3~+、CD4~+、CD4~+/CD8~+及NK细胞水平均显著高于对照组(P0.05)。结论:地佐辛治疗妇科肿瘤患者术后镇痛效果较好、安全性高,与芬太尼比较,其对机体的免疫抑制作用轻,更利于患者疾病的控制与康复,值得在临床应用推广。     

Redistribution of natural killer (NK) cell frequency and NK cytotoxic activity in primary IgA nephropathy.

Recent findings have indicated an imbalance of immune responsiveness in primary IgA nephropathy (IgAN). Thus natural killer (NK) cell frequency and NK cytotoxicity were evaluated in fifteen IgAN patients. CD8+, CD11+, CD56+ and CD57+ lymphocyte percentages in IgAN individuals fell within normal values, while a significant decrease of CD16+ cells was observed in the same group of patients. In contrast, NK activity overlapped that seen in controls as assessed by an agarose-single cell cytotoxic assay. To further investigate the discrepancy between CD16+ cell level and NK cytotoxic activity in IgAN, the proportion of CD11+ CD57+, CD56+ CD16+ and CD57+ CD16+ lymphocytes was determined. In spite of the unaffected CD56+ CD16+ cell frequency, IgAN subjects exhibited a significant decrease of CD11+ CD57+ and CD57+ CD16+ lymphocyte percentages in comparison to controls. It is suggested that a redistribution of NK lymphocyte subsets occurs in IgAN. This may have an important role in the impairment of the immunoregulatory network.     

Phenotype of peripheral blood leukocytes and survival of patients with metastatic colorectal cancer

Immune dysfunction is prevalent in metastatic cancer. Few patients with colorectal cancer metastases are cured, and among the strategies aimed at improving the therapeutic results in patients with metastatic colorectal cancer, immunotherapy is being increasingly investigated. We evaluated retrospectively the prognostic significance of peripheral blood leukocytes in 59 patients with metastatic colorectal cancer. The relative numbers of CD3+, CD3+CD4+, CD3+CD8+, NK (CD3-CD16+CD56+), CD3+DR+, CD3+CD25+, CD3+CD69+, CD19+, CD19+CD23+, CD8+CD28+, CD8-CD28+, CD8+CD57+, CD14+DR+ and CD14+CD16+ leukocytes were analyzed by two-color flow cytometry. A three-step approach was adopted to identify predictors of prognosis using regression analysis. Based on the results of univariate survival analysis, the absolute number of white blood cells, NK/CD3+CD69+ and NK/white cell count ratios were significant indicators of prognosis. In the multivariate regression analysis a model was obtained using a single parameter, the NK/CD3+CD69+ ratio, predicting the survival with 10-15% power of regression. The present results indicate that the NK/CD3+CD69+ ratio in peripheral blood may be an independent variable in a regression model predicting the overall survival of patients with colorectal cancer metastases to be tested in prospective studies.     

Immunoregulatory role of in vitro differentiated macrophages on human natural killer (NK)-cell activity

Immunoregulatory effects of human macrophages on natural killer (NK) activity were studied. Monocytes were isolated by adherence to plastic, after leukapheresis of normal blood donors, and cultured for 1 to 14 days. In vitro-differentiated (5-7 days) human macrophages consistently and significantly (P less than 0.01) augmented NK activity of fresh autologous or allogeneic PBMNC. During culture, these macrophages also developed increased antitumor cytostatic activity. The optimal time for both the expression of cytostatic activity and up-regulation of NK activity was 5-7 days in culture. In contrast, 12- to 14-day macrophages significantly suppressed NK activity and had less cytostatic activity. Macrophages in culture demonstrated shifts in Leu-M3+HLA-DR+ phenotype from the mean of 60% +/- 11 (SD) in fresh monocytes to 90% +/- 5 between Days 5 and 7 in culture and then down to 10% +/- 5 in 14-day cultures. The activity of NK (CD56+CD3-) cells, purified by Percoll gradient centrifugation and flow cytometry, was up-regulated directly by in vitro-differentiated macrophages at low macrophage to NK cell ratios, and this up-regulation was not dependent on T lymphocytes or other accessory cells. The modulation of NK activity by differentiated macrophages was not MHC-restricted and depended on the viability and cellular integrity of macrophages. Sonicated macrophages could no longer up-regulate NK activity. This study shows that antitumor effects mediated by human in vitro differentiated LeuM3+HLA-DR+ macrophages may simultaneously involve more than one mechanism, namely direct cytostasis of tumor cells and activation of NK cells.     

The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes

We examined the antigenic and functional characteristics of human peripheral blood lymphocytes that differentially express the CD16 (Leu-11) and Leu-19 (NKH-1) antigens. Leu-19 is a approximately 220,000 daltons protein expressed on approximately 15% of freshly isolated peripheral blood lymphocytes. Within the Leu-19+ subset, three distinct populations were identified: CD3-,CD16+,Leu-19+ cells; CD3+,CD16-,Leu-19+ cells; and CD3-,CD16-,Leu-19bright+ cells. Both the CD3+,CD16-,Leu-19+ and CD3-,CD16+,Leu-19+ populations mediated non-major histocompatibility complex (MHC)-restricted cytotoxicity against the NK-sensitive tumor cell K562 and were large granular lymphocytes. CD3-,CD16+,Leu-19+ NK cells were the most abundant (comprising approximately 10% of peripheral blood lymphocytes) and the most efficient cytotoxic effectors. The finding that CD3+,Leu 19+ lymphocytes mediated cytotoxicity against K562 unequivocally demonstrates that a unique subset of non-MHC-restricted cytotoxic CD3+ T lymphocytes are present in the peripheral blood of unprimed, normal individuals. However, CD3+,CD16-,Leu-19+ cells comprised less than 5% of peripheral blood lymphocytes, and the cytotoxic activity of this subset was significantly less than CD3-,CD16+,Leu-19+ NK cells. Most CD3+,Leu-19+ T cells co-expressed the CD2, CD8, and CD5 differentiation antigens. The antigenic and functional phenotype of peripheral blood CD3+,Leu-19+ cytotoxic T lymphocytes corresponds to the interleukin 2-dependent CD3+ cell lines that mediate non-MHC-restricted cytotoxicity against NK-sensitive tumor cell targets. A small population of Leu-19bright+ lymphocytes lacking both CD3 and CD16 was also observed. This population (comprising less than 2% of peripheral blood lymphocytes) contained both large agranular lymphocytes and large granular lymphocytes. CD3-,CD16-,Leu-19bright+ lymphocytes also mediate non-MHC-restricted cytotoxicity. The relationship of these CD3-CD16-,Leu-19bright+ lymphocytes to CD3+ T cells or CD16+ NK cells is unknown.     

Increase in CD3+ CD4- T lymphocytes in patients with AIDS and disseminated Mycobacterium avium-intracellulare complex infection: a prospective study. GECSA. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine

In a retrospective study, an increase in double-negative (CD3+ CD4- CD8-) (DN) T lymphocytes has been shown to be an independent predictor of disseminated Mycobacterium avium complex (D.MAC) infection in patients with less than 100 CD4+ T cells per mm3. To better characterize this cell expansion, a prospective study was designed. From July 1995 to April 1997, 206 HIV-infected patients with less than 100 CD4+ T cells per mm3 were prospectively followed up and immunophenotyped. The median followup was 1.1 year (+/-0.5 year), and 14 new D.MAC infections were diagnosed among 84 first AIDS-defining events. In univariate and multivariate analyses, D.MAC infections were the only opportunistic infection with a significant increase in DN T-cell percentage (median = 6.6; range = 1.7 to 24.5, P = 0.004) compared with patients without any opportunistic infection. This alteration in T-lymphocyte count could constitute a predictor for D.MAC infection in clinical practice.     

Activated and memory T lymphocytes in human milk.

Since activated macrophages and cytokines are found in human milk (HM), a flow cytometry study was conducted to determine whether T cells in HM display phenotypic markers of recent or previous activation. HM was collected during the first 3 d of lactation. The Paint-a-Gate program was used to optimize gating on the lymphocyte population. A mean +/- 1 SD of 4 +/- 3% of total HM leukocytes were lymphocytes and 96 +/- 3% were macrophages and granulocytes (N = 33 subjects). HM lymphocyte populations were further analyzed in five subjects. T cells (CD3+) represented 83 +/- 11% and B cells (CD19+) were 6 +/- 4% of HM lymphocytes. The mean CD4/CD8 ratio of T cells in HM was 0.88 (range 0.40-1.25). This ratio was significantly decreased compared to the peripheral blood (PB) of control adults (P less than 0.02) and postpartum women (P less than 0.02), due mostly to a significant increase in CD8+ CD3+ cells in HM compared to the PB of control adults (P less than 0.002) and postpartum women (P less than 0.05). T cells bearing markers of recent activation were significantly increased in HM compared to the PB of control adults: 85 +/- 7% of CD3+ cells in HM were HLA-DR+ (controls, 10 +/- 4%; P less than 0.001), and 15 +/- 6% of CD3+ cells in HM were IL-2R+ (controls, 6 +/- 2%; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

口腔鳞状细胞癌患者外周血Naa10及淋巴细胞免疫分型的特点及临床意义

目的探讨口腔鳞状细胞癌（OSCC）患者外周血N-α-乙酰基转移酶10 （Naa10）及淋巴细胞免疫分型的特点,并分析其临床意义。 方法选取97例OSCC患者及50名健康体检者,分别纳入患者组、对照组。检测两组受试者外周血Naa10、淋巴细胞免疫分型,并比较不同TNM分期、不同淋巴结转移状态患者外周血Naa10、淋巴细胞免疫分型的差异,总结其特点与临床意义。不同性别人数采用χ²检验,计量资料行正态性检验,满足正态性且组间方差相等则采用t检验,不满足正态性则采用非参数Wilcoxon秩和检验,相关性分析采用Pearson法。 结果患者组血清Naa10为（62.91±17.15）pg/ml,高于对照组的（38.82±9.04）pg/ml,差异有统计学意义（t?= 9.280,P?< 0.05）。患者组CD3⁺、CD4⁺、CD4⁺/CD8⁺、NK细胞百分比分别为（71.63±9.11）﹪、（34.34±4.26）﹪、（1.03±0.28）、（14.23±4.61）﹪,低于对照组的（76.25±2.87）﹪、（45.41±7.08）﹪、（1.77± 0.39）、（19.96±5.13）﹪,CD8⁺、B淋巴细胞百分比分别为（14.23±4.61）﹪、（14.91±3.29）﹪,高于后者的（19.96±5.13）﹪、（9.11±2.60）﹪,差异有统计学意义（P?< 0.05）。TNM分期Ⅰ~Ⅱ期患者42例,其血清Naa10为（64.08±15.26）?pg/?ml,与Ⅲ~Ⅳ期患者的（61.71±13.15）pg/ml比较,差异无统计学意义（t?= 0.820,P?> 0.05）。淋巴结转移者34例,其血清Naa10为（65.15±14.07）pg/ml,与无淋巴结转移者的（61.45±12.66）?pg/?ml比较,差异无统计学意义（t?= 1.321,P?> 0.05）。Ⅰ~Ⅱ期患者CD3⁺、CD4⁺、CD4⁺/CD8⁺、NK细胞百分比低于Ⅲ~Ⅳ期患者,其CD8⁺、B淋巴细胞百分比高于后者,差异有统计学意义（P?< 0.05）。Pearson相关性分析示,外周血Naa10与CD3⁺ （-0.631）、CD4⁺ （-0.529）、CD4⁺/CD8⁺ （-0.587）、NK细胞百分比（-0.603）呈负相关,与CD8⁺ （0.558）、B淋巴细胞百分比（0.670）呈正相关（P?< 0.05）。 结论OSCC患者外周血Naa10明显升高但与TNM分期、淋巴结转移无关;其淋巴细胞免疫分型存在明显改变,且TNM分期的上升、淋巴结转移的发生伴随着CD3⁺、CD4⁺、CD4⁺/?CD8⁺、NK细胞百分比的下降,以及CD8⁺、B淋巴细胞百分比的上升。     

康莱特配伍吉非替尼治疗对晚期非小细胞肺癌患者免疫功能和生活质量的影响

目的:评估康莱特(KLT)配伍吉非替尼治疗对晚期非小细胞肺癌(NSCLC)的免疫功能和生活质量的影响。方法:选取我院2013年1月-2014年7月诊治的晚期NSCLC患者64例并随机分为两组各32例。对照组给予吉非替尼口服,试验组在对照组基础上加KLT静脉滴注。观察两组T淋巴细胞亚群CD3~+、CD4~+、CD8~+、CD4~+/CD8~+表达情况及自然杀伤(NK)细胞活性;采用生活质量量表(QLQ-CCC)和卡式功能状态量表(KPS)对生活质量及功能状态进行评估。结果:试验组T淋巴细胞亚群CD4~+、CD4~+/CD8~+表达率及NK细胞活性高于对照组(P0.05),且其治疗前后的差值低于对照组(P0.05);试验组躯体、心理、社会、QLQ-CCC总分及KPS得分均高于对照组,且其治疗前后的差值均高于对照组(P0.05)。结论:KLT配伍吉非替尼治疗晚期NSCLC可减少吉非替尼对免疫功能的损害,提高患者的生活质量。     

Study of some lymphocyte subset counts and cytokine levels in cryptococcosis associated with AIDS

Approximately 100 new cases per year of cryptococcosis in HIV+ patients are observed in Mu?iz Hospital, 35% of them suffer a fatal outcome within the first four weeks after diagnosis in spite of treatment. Apparently there is not a useful parameter that allows a clear prediction of this early fatal outcome of the disease. The aim of this study is to determine some cytokine levels and several lymphocyte subpopulations counts in order to correlate these results with the evolution of the disease. Forty HIV+ patients suffering culture confirmed cryptococcosis were enrolled in this study, 8 HIV+ patients without cryptococcosis and 8 healthy individuals with negative serology for HIV were included as controls. The following determinations were done in all cases: CD3+, CD4+, CD8+, CD16+CD3-, CD19+ cell counts, IL-1; IL-12, TNFalpha in serum and TNFalpha in CSF. Ten cases with cryptococcosis and AIDS were controlled three months after treatment. The average of CD4+ and NK cell counts in patients before treatment were 22/microl and 90/microl respectively; IL-1 levels were higher in the patients than in the healthy control group, conversely IL-12 levels did not show significant differences in the three studied groups. Serum concentrations of TNFalpha were higher in patients than in the control group and were not modified after treatment, conversely antifungal medication diminished IL-1 concentration and remarkably increased NK cell counts. At the same time antigen levels in serum and CSF decreased. The results obtained seem to show that the immunological alterations observed in these patients are those characteristically exhibited in severe HIV disease and that some parameters such as CD8+ cell counts lower than 200/microl, less than 50 CD4+/microl, more than 50 pg/ml of TNF-alpha and serum capsular antigen titer higher than 1:5000 seem to predict a rapidly fatal course of infection.     

Bacterial activation of human natural killer cells. Characteristics of the activation process and identification of the effector cell

We showed previously that contact of human peripheral blood lymphocytes with glutaraldehyde-fixed Salmonella bacteria augmented their cytotoxic capacity against NK-sensitive targets. We have now analyzed the characteristics of the activation and also identified the subsets of lymphocytes responding to bacterial contact. Blocking of protein synthesis with cyclohexamide totally abrogated bacterial induction of activated killing (AK), whereas inhibition of DNA synthesis with mitomycin C did not significantly affect the capacity of lymphocytes to respond to bacterial contact. Both the induction and the effector phase of AK were radioresistant. The AK cells exhibited efficient lytic activity, comparable to that induced by recombinant IL 2 (rIL 2), against NK-resistant targets (including both hematopoietic and solid tumor cell lines). All inducible cytotoxic activity was contained within the subset of lymphocytes expressing Leu-19 (NKH-1) antigen. Leu-19- lymphocytes exhibited no significant NK activity and could not be further stimulated by bacterial contact, rIL 2, or IFN-alpha. Within the Leu-19+ lymphocyte subset, two distinct cell types were present; CD3-, Leu-19+ NK cells and CD3+. Leu-19+ T cells. The CD3+, Leu-19+, T cells mediated low levels of non-MHC-restricted cytotoxicity against K562, but did not respond to bacterial contact, even though rIL 2 could augment their lytic activity slightly. However, the cytotoxic activity of CD3-, Leu-19+ NK cells was significantly augmented by bacterial contact. Within the CD3-, Leu-19+ NK cell population both CD16+ and CD16- cells responded to bacterial activation. The CD3-, CD16-, Leu-19+ cells constituted 1 to 4% of the Percoll-fractionated low buoyant density lymphocytes and accounted for the activation seen within the CD16- lymphocyte population. Thus bacterial stimulation of NK activity seems to be mediated for the most part via CD16+, Leu-19+ cells, and a minor overall contribution is mediated via CD3-, CD16-, Leu-19+ cells. No apparent involvement of T cells was seen in the lytic response of lymphocytes to bacterial contact.