严重急性呼吸综合征患者淋巴细胞亚群的动态变化及意义

目的　了解成人严重急性呼吸综合征 (SARS)患者淋巴细胞亚群的改变对疾病的发生、发展及预后的影响。方法　依据卫生部颁发的传染性非典型肺炎临床诊断标准及预后将 2 0 6例SARS患者分为 3组 :即非重症组 13 3例、重症存活组 50例、重症死亡组 2 3例 ,用流式细胞仪进行淋巴细胞亚群CD4+、CD8+、CD19+、CD16+淋巴细胞的动态检测。建立数据库并对检测结果进行统计学分析。结果　SARS患者CD4+、CD8+、CD19+淋巴细胞计数均值分别是非重症组 >重症存活组 >重症死亡组 ,组间比较均P <0 .0 5。CD16+均值非重症组与重症存活组比较P >0 .0 5,两组与死亡组比较均P <0 .0 1。通过对CD4+、CD8+、CD19+、CD16+淋巴细胞计数动态观察 ,发现非重症组与重症存活组随病程CD4+、CD8+先下降后上升 ,CD19+随病程逐渐上升 ,CD 16+在发病早期有短暂的升高 ,然后波动在正常范围内。重症死亡组CD4+、CD8+、CD19+、CD16+在发病初期即处于较低水平 ,发病 15d后CD4+、CD8+、CD19+仍持续低水平 ,而CD16+随病程呈持续性降低。结论　成人SARS患者有明显的细胞免疫损伤 ,其淋巴细胞亚群的改变与临床分型及预后相关 ,对预后判断有一定的指导意义。SARS患者CD4+、CD8+淋巴细胞计数在发病初期是降低的 ,非重症组、重症存活组发病 9～15d是最     

Morbidity and mortality in rheumatoid arthritis patients with prolonged therapy-induced lymphopenia: twelve-year outcomes

OBJECTIVE: To assess immunologically relevant outcomes in a cohort of rheumatoid arthritis (RA) patients with prolonged therapy-induced lymphopenia. METHODS: Morbidity (infection or malignancy) and mortality were assessed in 53 RA patients who were treated with the lymphocytotoxic monoclonal antibody alemtuzumab between 1991 and 1994. Data were obtained by interview, medical record review, and Office for National Statistics mortality monitoring. Lymphocyte subsets were enumerated by flow cytometry. A retrospective, matched-cohort study of mortality was performed with 102 control subjects selected from the European League Against Rheumatism database of patients with rheumatic disorders. RESULTS: Lymphopenia persisted in the patients: median CD3+CD4+, CD3+CD8+, CD19+, and CD56+ lymphocyte counts measured at a median followup of 11.8 years from the first administration of alemtuzumab were 0.50 x 10(9)/liter, 0.26 x 10(9)/liter, 0.11 x 10(9)/liter, and 0.09 x 10(9)/liter, respectively. Twenty-seven of 51 cases and 46 of 101 controls with available data had died, yielding a mortality rate ratio of 1.20 (95% confidence interval 0.72-1.98). Causes of death were similar to those that would be expected in a hospital-based RA cohort. No opportunistic infections were noted, and only 3 infections were documented following 36 elective orthopedic procedures. CONCLUSION: Despite continued lymphopenia 11.8 years after therapy, our patient cohort did not exhibit excess mortality or unusual infection-related morbidity, and surgery was well tolerated. These data should be reassuring for clinicians and patients who are considering lymphocytotoxic or other immunomodulatory therapy for RA.     

Early activation of peripheral lymphocytes in human acute pancreatitis

BACKGROUND: The CD69 antigen is an indicator of early lymphocyte activation. GOALS: To evaluate the early activation of peripheral lymphocytes T, B, and NK in patients with acute pancreatitis in comparison with patients with acute abdomen of nonpancreatic origin. STUDY: Thirty patients with acute pancreatitis were studied; 20 of them had the mild form of the disease and 10 had the severe form. Thirty patients with nonpancreatic acute abdomen were used as controls. All patients were enrolled within 48 hours of the onset of pain. In all patients, leukocytes and total lymphocyte and lymphocyte subset counts (CD4+, CD8+, CD56+, CD19+, CD4+CD69+, CD8+CD69+, CD56+CD69+, CD19+CD69+) were determined upon hospital admission. RESULTS: The percentage of total lymphocytes was significantly lower in acute pancreatitis patients than in those with nonpancreatic acute abdomen (P = 0.014); patients with severe pancreatitis had a percentage of total lymphocytes significantly lower when compared with patients with mild pancreatitis (P < 0.001). The CD19+CD69+ count was significantly lower in patients with severe pancreatitis (24.6 +/- 14.6%) than in patients with mild pancreatitis (46.7 +/- 16.5%; = 0.006). The counts of the other lymphocyte subsets were not statistically different between patients with acute pancreatitis and those with nonpancreatic acute abdomen, as well as between patients with mild and severe acute pancreatitis. CONCLUSIONS: Patients with severe pancreatitis show impaired early activation of peripheral CD19+ cells.     

Serum LD1 isoenzyme and blood lymphocyte subsets as prognostic indicators for severe acute respiratory syndrome

BACKGROUND: The pathophysiology of severe acute respiratory syndrome (SARS) is at present poorly understood, but advanced age and serum total lactate dehydrogenase (LD) activity >300 U L(-1) have been associated with adverse clinical outcomes. Blood leucocytes and lymphocyte subsets were reported to decrease, respectively, in 47% and up to 100% of 38 patients in Beijing. However, their prognostic implications have not been thoroughly investigated. OBJECTIVE: To investigate serum total LD, LD isoenzymes, and other parameters including blood lymphocyte subsets as prognostic indicators in SARS patients for adverse clinical outcomes in terms of admission to intensive care unit (ICU) and death. DESIGN: Retrospective analysis. SUBJECTS AND METHODS: A total of 109 patients with a clinical diagnosis of SARS according to the modified World Health Organization case definition of SARS were recruited from two major acute hospitals in Hong Kong. They were either involved in the initial outbreak of SARS, or cases from the community outbreak of Amoy Gardens between 10 March and 5 May 2003. The clinical diagnosis was subsequently confirmed by serological test and/or molecular analysis. Serum total LD and LD isoenzyme activities, complete blood picture with total leucocyte count and differential counts, absolute counts of CD3+, CD4+, CD8+, natural killer cells and B lymphocytes were measured daily upon admission. Receiver operating characteristic curve analysis was used to determine and compare different cut-offs for various biochemical and immunological parameters at peak serum total LD concentration in predicting adverse clinical outcomes. RESULTS: Of a total of 109 patients, 41 were admitted to ICU and 42 died. Of 42 fatal patients, 24 died in ICU and 18 died in general medical wards. Age was found to be an independent prognostic indicator for death with an area under curve (AUC) of 0.96 [95% confidence interval (CI) = 0.90-0.99] but not for admission to ICU [AUC = 0.61 (CI = 0.51-0.70)]. Whilst serum total LD could only achieve AUC of 0.68 (CI = 0.59-0.77) for predicting death, LD1 isoenzyme was found to be the best biochemical prognostic indicator with AUC of 0.84 (CI = 0.75-0.90), sensitivity of 62% (CI = 46-76%), specificity of 93% (CI = 83-98%) at cut-off activity of > or =80 U L(-1). CD3+, CD4+, CD8+ and natural killer cell counts were promising immunological prognostic indicators for predicting admission to ICU with AUC of 0.94 (CI = 0.86-0.98), 0.91 (CI = 0.81-0.96), 0.93 (CI = 0.85-0.98), and 0.87 (CI = 0.76-0.94), respectively. CONCLUSIONS: Apart from age, serum LD1 activity was the best prognostic indicator for predicting death in patients with SARS compared with serum total LD activity, haemoglobin concentration, leucocyte and lymphocyte counts. Its release could possibly be from blood erythrocytes and body tissues other than the myocardium. Blood CD3+, CD4+, CD8+ and natural killer cell counts were found to be good prognostic indicators for predicting admission to ICU in patients with SARS compared with age, leucocyte count and LD isoenzymes. The suppressed CD3+, CD4+, CD8+, and natural killer cell counts were also implicated in the pathophysiology of SARS. Patients with increased serum LD1 should be closely monitored to ensure prompt management, and preparation for admission to ICU could be planned ahead for patients with suppressed lymphocyte subsets.     

Thoracoscopic talc poudrage decreases T-lymphocytes in the peripheral blood

BACKGROUND: Thoracoscopic talc poudrage induces peripheral blood granulocytosis and lymphopenia. The aim of this study is to investigate the type of lymphopenia in patients undergoing thoracoscopic talc poudrage. METHODS: We have measured peripheral blood lymphocyte subsets in 11 patients undergoing thoracoscopic talc poudrage, before (baseline), at 24 and 48 h after the procedure. Lymphocyte numbers were analysed by flow cytometry for the evaluation of the CD3+, CD4+, CD8+ cells (total T-lymphocytes, helper T-lymphocytes, cytotoxic T-lymphocytes, respectively), the CD19+ cells (B-lymphocytes), and the CD16+, CD56+ and CD57+ cells (NK-cells). No anti-inflammatory medication was permitted before, during or after the procedure. RESULTS: Absolute peripheral blood lymphocyte count significantly decreased following thoracoscopic talc poudrage compared to baseline values (p=0.007). Similarly, peripheral blood CD3+, CD4+ and CD8+ lymphocyte counts significantly decreased compared to baseline (p=0.005, 0.02 and 0.03, respectively) with a more prominent reduction of CD3/CD45RO memory cells. No significant difference was found in the absolute number of CD19+, CD16+, CD56+, and CD57+ cells before and after thoracoscopic talc poudrage. CONCLUSION: Patients undergoing thoracoscopic talc poudrage display peripheral blood T-lymphopenia following the procedure.     

Assessment of peripheral blood lymphocyte subsets in idiopathic myelofibrosis

The objective of this study was to contribute to a better characterization of the immunological profile of idiopathic myelofibrosis (IM) at presentation by analysing the blood lymphocyte subsets and their possible correlations with other disease features. Absolute blood lymphocytes and lymphocyte subsets were assessed in 31 IM patients, compared with those from 34 healthy individuals, and correlated with the patients' main clinical, hematological and bone marrow histologic features. The mean lymphocyte count of the IM patients was 1.1 (SD 0.6) x 10(9)/L, versus 1.6 (SD 0.49) x 10(9)/L in controls (p = 0.0006), with 24 of the 31 patients (77.4%) showing lymphocytopenia (< 1.5 x 10(9)/L). IM patients had significantly lower counts of CD3, CD4, CD8, and CD3 -/ CD56+ cells, and significantly higher CD3 +/CD56 + lymphocyte counts. Although no significant differences were found between patients and controls with regard to CD19+/CD5+ cell counts, increased CD5 + B-cell lymphocytes were observed in three IM patients. In one of the latter patients, Ig gene rearrangement analysis of the heavy chain gene demonstrated such a subpopulation to be clonal, but the patient did not develop features of chronic lymphoid leukemia during a 5-yr follow-up. No correlation was found between the patients' blood lymphocyte counts and other disease features. We conclude that most IM patients have absolute lymphopenia, decreased T cells and increased cytotoxic T cells at diagnosis, and 10% of them show an increased CD5 + B-cell subpopulation.     

Exercise-induced CD8 lymphocytosis: a phenomenon associated with large granular lymphocyte leukaemia

This report describes a patient with a large granular lymphocyte leukaemia (CD8 + lymphoproliferative disease) and severe neutropenia (less than 0.5 x 10(9)/l) in whom exercise resulted in a marked lymphocytosis, a phenomenon which has not previously been recorded. The lymphocyte count at rest was within normal limits (2.2 x 10(9)/l), then fell to the resting level within 15 min of cessation of exercise. The peripheral blood mononuclear cells showed the morphology of large granular lymphocytes (LGL) by light and electron microscopy both at rest (30%) and to a much greater extent during exercise (70%). Immunophenotyping of these lymphocytes during exercise demonstrated that the predominant cell was CD3+, CD8+, CD57+ (Leu7)/CD4-, CD16-, CD25-. In the resting state, despite a total lymphocyte count within the normal range, surface marker studies indicated an excess of cells with the CD8+/CD57 + T cell phenotype (26%; cf. normal range less than or equal to 10%). Functional assays revealed a minimal increase in natural killer (NK) activity during exercise. T cell receptor beta chain gene rearrangement was demonstrable in the peripheral blood at rest and during exercise. Although severe neutropenia was present, the growth of normal colony forming units, granulocyte-macrophage (CFU-GM) was not inhibited by patient lymphocytes and no anti-neutrophil antibodies were demonstrated. Finally, hyposplenism has developed and the relationship of this to the LGL leukaemia is discussed. In summary, the findings demonstrated large granular lymphocyte leukaemia as the primary disorder for which the primary manifestation, apart from the neutropenia, was a marked exercise-induced lymphocytosis.     

阿苯达唑治疗前后泡状棘球蚴病患者淋巴细胞亚群变化及临床意义

目的　探讨泡球蚴病患者经阿苯达唑治疗后 ,机体免疫应答的状态和对病程转归的影响。　方法　 7例未治疗泡球蚴病患者 ,6例经阿苯达唑治疗 12个月泡球蚴病患者 ,6例经阿苯达唑治疗 2 4个月泡球蚴病患者和 18例非流行区健康人群 ,用 FCM分析了 CD3+ 、CD4 + 、CD8+ 、CD1 9+ 、CD38+ 、CD1 6 + 56 + 和 HL A- DR+ 细胞的数量。　结果　治疗 12个月后 ,患者 CD8+细胞数继续上升 (P<0 .0 1) ,CD4 + / CD8+比值进一步倒置 ;治疗 2 4个月后 ,CD4 +细胞数开始升高 (P<0 .0 5 ) ,CD8+ 细胞数下降 ,CD4 + / CD8+ 比值升高 (P<0 .0 5 ) ;CD1 9+ 细胞在治疗 2 4个月后显著性升高 (P<0 .0 5 ) ;CD38+ 和 HL A-DR+ 细胞在治疗 2 4个月后呈显著性下降 (P<0 .0 1)。　结论　泡球蚴病患者治疗后 ,CD8+ 细胞引起的免疫抑制状态有所减轻 ,机体的保护性免疫应答有所恢复。     

Lymphocyte count and mortality risk in older persons. The Leiden 85-Plus Study

OBJECTIVES: To investigate whether a low peripheral blood lymphocyte count is associated with increased mortality risk in older persons and to determine whether this association could be ascribed to ill health. DESIGN: A cohort study with a total follow-up period of 1,602 person years. SETTING: Leiden, the Netherlands. PARTICIPANTS: Four hundred thirty-six community-dwelling residents aged 85 and older. MEASUREMENTS: Health status and leukocyte total and differential counts were assessed at baseline. Lymphocyte subsets were measured with a fluorescence-activated cell sorter. Age- and sex-adjusted mortality risks were estimated using Cox proportional hazard regression analysis. RESULTS: There was no association between lymphocyte count and mortality in persons with ill health (mortality risk lowest vs highest quartile=1.16; 95% confidence interval (CI)=0.85-1.58, P=.35), but mortality was dependent on lymphocyte count if disease was excluded (mortality risk lowest vs highest quartile=2.14; 95% CI=1.08-4.23, P=.03). A similar increase in mortality risk was found when the cluster designation (CD)4+, CD8+, and CD16+ lymphocyte subsets were analyzed. Within individuals, low values of the lymphocyte subsets were related and there was no compensatory increase in CD16+ lymphocyte counts. A low lymphocyte count was not associated with specific causes of death. CONCLUSION: A low lymphocyte count was associated with an increased mortality risk in older persons without apparent disease. This association was not only found for the total lymphocyte count but also for the CD4+, CD8+, and CD16+ lymphocyte subset counts.     

结核病小鼠T淋巴细胞亚群及其表达的四项细胞因子分析

目的 探讨T淋巴细胞(简称T细胞)表达穿孔素(PFN)、颗粒酶B(GzmB)、γ-干扰素(IFN-γ)、白细胞介素-2(IL-2)与结核免疫的关系.方法 60只MK小鼠按随机数字表法分成结核病组和健康对照组,每组30只.以CD3PerCP、CD4FTTC、CD8APC单抗标记T细胞亚群,以藻红蛋白标记PFN、GzmB、IFN-γ、IL-2单抗标记细胞因子,以流式细胞仪检测分析总的淋巴细胞、CD3+、CD4+、CD8+、CD4+CD8+;双阳(DP)T细胞计数和各亚群占淋巴细胞百分率,观察各T细胞亚群内表达PFN、GzmB、IFN-γ、IL-2的阳性细胞计数和各自占淋巴细胞百分率.采用t检验进行统计学分析.结果 (1)CD4+CD8+、DP T细胞均能不同程度地表达PFN、GzmB、IFN-γ、IL-2.PFN、GzmB的表达以CD8+T细胞占优势.IFN-γ、IL-2的表达以CD4+T细胞占优势.(2)T细胞亚群细胞计数结果与T细胞亚群占总淋巴细胞百分率结果,所反映的T细胞免疫变化趋势可能相似,也可能不同甚至相反.(3)两组间表达PFN的T细胞差别不明显,但结核病组表达GzmB的各个T细胞亚群计数和CD3+%、CD8+%、DP%高于对照组(t值为-3.72～4.13.均P<0.05).(4)结核病组表达IFN-γ的CD3+、CD4+T细胞计数高于对照组;但结核病组表达IL-2的CD8+、DP T细胞计数和CD3+%、CD4+%、CD8+%、DP%均低于对照组(t值为2.62～3.46,均P<0.05).结论 、CD,4+、CD8+、DPT细胞均能不同程度地表达PFN、GzmB、IFN-γ、IL-2;联合评价T细胞各亚群计数和其占淋巴细胞百分率更能判断免疫学状态.     

CD4+ and CD8+ lymphocytes and HIV RNA in HIV infection: high baseline counts and in particular rapid decrease of CD8+ lymphocytes predict AIDS

OBJECTIVE: To study the progression of HIV infection in relation to immunological and virological variables with emphasis on the role of CD8+ lymphocytes. DESIGN: Prospective follow-up from October 1991 of patients observed for at least 18 months allowing nucleoside analogue monotherapy. Peripheral CD4+ and CD8+ lymphocyte counts, HIV RNA, and soluble CD8 were analysed by statistics allowing the evaluation of serial data, avoiding time points with concurrent infections. SETTING: Tertiary university clinic. PATIENTS: Forty-nine patients were followed for 52.6 months, baseline CD4+ count of 300 x 10(6)/l, sample interval of 5.9 months (medians). MAIN OUTCOME MEASURES: AIDS, death, and CDC groups B- or C-related events. RESULTS: AIDS developed in 28% of patients. Baseline CD8+ counts above the median were significantly associated with AIDS development; the best Cox model included CD8+ cells and the log10RNA/CD4 ratio. A decline in CD8+ counts relative to baseline most significantly predicted AIDS, along with higher baseline RNA and actual CD4+ counts of less than 200 x 10(6)/l. Levels of soluble CD8 in the blood relative to total CD8+ cells significantly increased in patients developing AIDS. Death occurred in 16% of the patients, and was only predicted by high CD8+ cell counts at baseline. CDC B- and C-related events occurred in 35% of the patients and were best predicted by high baseline CD8+ counts and high RNA levels. CONCLUSIONS: The serial quantitation of CD8+ lymphocytes gave highly significant predictive information on the natural progression of HIV infection in patients with moderate to severe immune deficiency. Our data suggest that the hyperactivation of CD8+ lymphocytes is an important factor leading to a numerical decrease of CD8+ lymphocytes in progressive HIV infection.     

大强度运动对大鼠脾脏淋巴细胞、巨噬细胞、T淋巴细胞亚群的影响

目的探讨大强度运动对大鼠脾脏淋巴细胞、巨噬细胞、T淋巴细胞亚的影响。方法40只SD大鼠按体重随机分为安静组(A组,n=10)、运动组(B组,n=30),在最后一次力竭运动后,将B组大鼠分为运动后即刻组(B 1组,n=10)、运动后12 h组(B 2组,n=10),运动后24 h组(B 3组,n=10)。A组不运动,B组大鼠进行为期9 w的大强度训练,末次训练后,A组、B 1组摘取脾脏,制作脾细胞悬液,噻唑蓝(MTT)法分别测T淋巴细胞增殖能力、B淋巴细胞增殖能力,流式细胞仪测CD4^+、CD8^+细胞数。中性红比色法测巨噬细胞吞噬能力。B 2组、B 3组分别在运动后12 h、运动后24 h按上述方法测试。结果与A组相比,B 1组T淋巴细胞增殖、B淋巴细胞增殖、CD4^+、CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力显著降低,B 2组T淋巴细胞增殖、B淋巴细胞增殖、CD4^+、CD4^+/CD8^+显著降低,巨噬细胞吞噬能力差异无统计学意义,B 3组T淋巴细胞、B淋巴细胞增殖能力、CD4^+、CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力差异无统计学意义;与B 1相比,B 2组、B 3组T淋巴细胞增殖、B淋巴细胞增殖、CD4^+、CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力显著升高;与B 2相比,B 3组T淋巴细胞增殖、B淋巴细胞增殖、CD4^+均显著升高,CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力无显著差异。结论大强度运动后,大鼠脾脏、B淋巴细胞、T淋巴增殖能力降低、巨噬细胞吞噬能力降低、CD3^+、CD4^+、CD8^+、CD4^+/CD8^+降低,恢复期间逐步上升,其中CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力在恢复期12 h基本达到正常状态,T淋巴细胞增殖能力、B淋巴细胞增殖能力、CD4^+在恢复期24 h达到正常状态。     

HIV／AIDS患者血浆病毒载量及外周血T淋巴细胞亚群的变化

目的：观察国内HIV／AIDS患者血浆病毒载量和外周血CD4^ 、CD8^ T淋巴细胞的变化，探讨这些变化的临床意义。方法：选择未经抗病毒治疗的HIV／AIDS患者124例，用bDNA法检测血浆病毒载量，并用流式细胞仪检测外周血CD4^ 、CD8^ T淋巴细胞。结果：AIDS患者的血浆病毒载量明显高于HIV感染者，血浆病毒载量与CD4^ 细胞计数呈显著负相关，但其最高峰位于CD4^ 细胞计数100／μl处，然后随着CD4^ 细胞计数的下降而减少。CD4^ T细胞计数为AIDS组＜HIV组＜正常对照组：HIV感染者的CD8^ T细胞计数显著高于正常组和AIDS组，而AIDS患者CD8^ T细胞数则随着CD4^ T细胞减少而下降。结论：血浆病毒载量随着疾病进展而显著升高，但在疾病晚期则有所降低。外周血CD4^ T细胞计数随着疾病的进展而进行性减少；CD8^ T细胞计数在感染早期显著升高，进入晚期则减少。在评价HIV感染者和AIDS患者病情时，应结合病毒载量、CD4^ 、CD8^ T细胞计数综合分析。     

Effect of age on human immunodeficiency virus type 1-induced changes in lymphocyte populations among persons with congenital clotting disorders. Transfusion Safety Study Group.

Children other than neonates infected with human immunodeficiency virus type 1 (HIV-1) have low rates of progression to acquired immunodeficiency syndrome (AIDS). Through 1989, 5.3% of 95 infected hemophiliacs aged 5 to 13 years developed AIDS, compared with 20.3% of 364 aged greater than or equal to 25 years. We asked whether the HIV-1 impact on peripheral blood mononuclear cell subpopulations differed with age using pairwise comparisons of uninfected and infected male children and adult hemophiliacs. Infected children had lesser reductions of total lymphocytes than adults, but proportionately lower numbers of CD2+, CD4+, CD2+CD26+, and CD4+CD29+ counts. CD4+CD45RA+ cell counts were greater than twofold higher in uninfected and infected children than adults; with infection, the CD4+CD45RA+/CD4+ proportion increased by 1.4-fold in adults, but was unchanged in children. Infected adults had highly significantly increased total CD8+ counts; both age groups had elevated CD8+HLA-DR+ counts. Infected children had significantly higher total B-cell counts than infected adults, with a disproportionately lower number of resting B cells (CD20+CD21+). During 2 years of follow-up, infected children and adults had lymphocyte changes in the same directions and these were proportionately equal. The lower rate of HIV-1 progression in children may be partly associated with differences in lymphocyte populations compared with adults; functional properties of immune cells may be equally or more important.     

Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group.

OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.     

Immunomodulatory effects of secondary hyperparathyroidism on circulating CD4+ and CD8+ T-lymphocytes in chronic renal failure patients

The immunomodulatory effects of parathyroid hormone (PTH) in patients with end stage renal disease (ESRD) is controversial. This study was carried out to investigate the effect of PTH levels on the circulating CD4+, CD8+ T cell counts (%) in patients with chronic renal failure (CRF) on regular hemodialysis ((HD). The study included 22 patients with serum levels of PTH < 300 pg/ml (group 1), 18 patients with PTH > 300 pg/ml (group II) and 10 age and sex matched normal controls (group III). Chemiluminescence and flowcytometry assays were performed for determination of serum PTH levels and T cell subset counts respectively. The mean (%) of total lymphocyte, CD4+, CD8+ and CD4\CD8 ratio of group I were (81.68+/- 9.38), (52.00+/-6.24), (27.13+/- 6.31) and (1.99+/-0.42) respectively, as compared to (73.83+/-13.30), (46.05+/-8.59), (23.05+/-4.63) and (2.03+/-0.41) respectively in group II. Values of group I and II were significantly (P<0.001) lower than controls (88.50 +/- 6.02), (63.30 +/- 6.44), (36.80 +/- 6.44) and (1.76+/-0.36) respectively. In group II, the reduction was significantly (P<0.001) prominent in patients with high PTH levels, with significant inverse correlations (P<0.001) between PTH and % of total lymphocyte (r= -0.93), CD4+ (r= -0.74) and CD8+ % (r=-0.69). In conclusion, increased level of PTH in CRF patients on hemodialysis is associated with lymphopenia and reduction in CD4+ & CD8+ subsets of T cells. Monitoring circulating PTH levels in such patients can restore their immune competence.     

Immune reconstitution after haematopoietic cell transplantation in children: immunophenotype analysis with regard to factors affecting the speed of recovery

Immune reconstitution was studied prospectively in 66 children who underwent 77 haematopoietic cell transplantations (HCT): 46 autologous HCTs in 39 patients and 31 allogeneic HCTs in 27 patients. We studied the dynamic analysis of immune recovery with regard to potential factors affecting its speed, including age, type of HCT, diagnosis, graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection reactivation. Absolute counts of different lymphocyte subsets and immunoglobulin serum levels were determined in peripheral blood of patients on d -7 and +16, and then at various intervals up to 24 months post transplant. Common patterns of immune recovery after both allogeneic and autologous HCT were identified: (i) CD4+CD45RO+ peripheral T-cell expansion on d +16; (ii) inverted CD4+:CD8+ ratio from d +30 onwards; (iii) rapid natural killer (NK) cell (CD16+/-CD56+) count normalization. We observed prolonged T-cell lymphopenia (CD3+, CD3+CD4+, CD4+CD45RA+) until 24 months after autologous HCT, whereas in the allogeneic setting CD3+CD4+ cells, including naive CD45RA+ cells, returned to normal values at 9 months post transplant. Age > 10 years and coexistence of GvHD and CMV reactivation were associated with a substantial delay in T- (CD4+, including CD45RA+) and B-cell recovery after allogeneic HCT. Multidrug GvHD prophylaxis resulted in impaired T- (CD4+, CD4+CD45RA+) and B-cell reconstitution only in the early phase after allogeneic HCT (up to 4 months). Our results demonstrated that T-cell recovery was severely impaired in children after autologous HCT. It should be emphasized that specific approaches to enhance immune reconstitution are necessary to control minimal residual disease and avoid the risk of infectious complications in the autologous setting. Thymic involution after allogeneic HCT seems to be associated with age and coexistence of GvHD and CMV reactivation.     

Growth hormone (GH)-induced reconstitution of CD8+ CD28+ T lymphocytes in a rare case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's syndrome

This paper describes a rare case of Turner's syndrome associated with Juvenile Haemochromatosis and severe lymphopenia, followed-up for a period of 5 years. Because of the indication for treatment with growth hormone (GH), this case was observed as a model to analyse the effects of GH on growth, iron mobilization and lymphocyte reconstitution. For this purpose, a serial study of the T lymphocyte subpopulations CD4+, CD8+, CD8+ CD28+ and CD8+ CD28- was performed by immunophenotyping during the follow-up period. Besides the impact of both phlebotomy treatment and GH on the rapid growth and mobilization of 20.8 g of iron in 136 weeks, the most relevant observation was the finding of a significant expansion of CD8+ T lymphocytes expressing the costimulatory marker CD28 in the setting of the severe lymphopenia. These findings constitute new clinical evidence supporting the notion that the GH/IGF-1 system has an important role on the maintenance of T cell homeostasis in vivo, and that GH may be regarded as a putative therapeutic agent in T lymphocyte reconstitution.     

Immunological alterations associated with Plasmodium vivax malaria in South Korea

Various haematological and immunological studies on patients infected with Plasmodium vivax were undertaken, at diagnosis (day 0), after treatment with chloroquine but during primaquine treatment (day 10) and after all treatment (day 59), in South Korea (where there has been a recent and abrupt increase in the incidence of such infection). The main aims were to gain an understanding of the haemto-immunological alterations of this malarial infection, both before and after treatment, and to identify at least one useful marker for the diagnosis and post-treatment monitoring of P. vivax malaria. Thirty-eight patients with P. vivax malaria were compared with 20, apparently healthy controls. At diagnosis, the patients had lymphopenia, marked eosinopenia (the eosinophil count being correlated with the platelet count) and thrombopenia. Cells of most of the lymphocyte subsets investigated [i.e. CD3+, CD8+, CD19+, CD56+, CD3-/CD56+ and CD8+/CD56+ but not CD4+, CD3+/CD56+ or CD25+] were significantly less common among the lymphocytes of patients at diagnosis than among those of the controls. After initiating treatment, the numbers of CD19+ lymphocytes gradually increased (to normal values by day 59), whereas those of CD3+/56+ lymphocytes remained abnormally low throughout the follow-up period. The proportions of lymphocytes identified as CD4+ appeared to be unaffected by treatment. Although serum concentrations of IgE (and, to a lesser extent, IgM) were elevated in the patients at diagnosis, they were subnormal on day 10 post-treatment and normal at the day-59 follow-up. Serum concentrations of IgG and IgA in the patients were always found to be similar to those in the controls. At diagnosis the serum concentrations of complements C3 and C4 were significantly elevated in the patients. C3 remained at the same high concentration during follow-up but the concentration of C4, like that of IgE, was found to be subnormal on day 10 and normal 7 weeks later. The level of parasitaemia (%) was only found to be significantly correlated with haemoglobin concentration. The observation of eosinopenia with elevated IgE and C4 could be a useful indicator of P. vivax malaria, and treatment response could be followed by serial monitoring of serum concentrations of IgE and C4.     

93例传染性非典型肺炎患者外周血T淋巴细胞亚群变化及临床意义

目的　了解传染性非典型肺炎 (世界卫生组织又称严重急性呼吸综合征 ,SARS)患者外周血T淋巴细胞亚群的变化。方法　采用流式细胞仪对 93例临床确诊的SARS患者、5 0例获得性免疫缺陷综合征 (AIDS)患者及 6 4例健康体检者外周血T淋巴细胞亚群进行检测。 93例患者中 ,男4 0例、女 5 3例 ;年龄 17～ 88岁 ,平均 4 4岁 ;重型 35例、普通型 5 8例。结果　健康体检者外周血CD+ 3 、CD+ 4 、CD+ 8分别为 (15 2 7± 4 70 )、(787± 2 5 7)、(6 33± 2 80 )个 / μl;93例急性期SARS患者分别为(72 2± 5 33)、(438± 35 3)、(30 7± 2 17)个 / μl,均有不同程度的下降 (P值均 <0 .0 1) ,重症病例下降尤其明显 ,5例死亡患者外周血CD+ 4 均低于 2 0 0个 / μl;SARS患者恢复期CD+ 3 、CD+ 4 、CD+ 8多数恢复正常。而AIDS患者以CD+ 4 降低为主 ,为 (2 96± 2 98)个 / μl;且CD+ 8升高 ,为 (818± 5 6 6 )个 / μl。 结论SARS患者有明显的细胞免疫损伤。