Morphological variants of leukemic cells in B chronic lymphocytic leukemia are associated with different T cell and NK cell abnormalities

B chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease. The different morphological variants of leukemic B cells appear to define different clinical groups of patients. Several abnormalities have been found in T lymphocytes and natural killer (NK) cells from B-CLL patients. We have investigated the phenotypic and functional characteristics of purified CD2+ cells from B-CLL patients at Binet's stage A and classified according to the neoplastic B lymphocyte morphology criteria: 32 patients with typical B-CLL and 12 patients with atypical B-CLL. Forty-three age and sex matched healthy controls were also studied. In fresh purified CD2+ cells from typical B-CLL patients, percentages of CD4+, CD4+CD45RA+, CD8+CD45RA+ T lymphocytes and CD3−CD56+ (NK) cells were significantly higher than those found in atypical B-CLL patients. However, in DC2+ cells from typical B-CLL patients, percentages of CD3+, CD3+DR+, CD8+, CD4+CD45RO+, and CD3+CD56+ cells were significantly lower than those found in atypical B-CLL patients. Increased percentage of NK cells was only found in typical B-CLL patients. The proliferative response and the production of interleukin (IL)-2 and IL-4 by phytohemagglutinin (PHA) stimulated CD2+ cells were significantly higher in typical B-CLL patients than in atypical B-CLL patients. We concluded that different patterns of phenotypic and functional alterations in the T lymphocytes and NK cells of B-CLL patients are found in patients with typical or atypical B-CLL defined according to the morphology of the leukemic cells. Am. J. Hematol. 55:175–182, 1997. © 1997 Wiley-Liss, Inc.     

T-cell activation and subset patterns are altered in B-CLL and correlate with the stage of the disease

Two-color FACS analysis was used to study activated and "functional" T and natural killer (NK) cell subsets of circulating lymphocytes in 23 patients with B-type chronic lymphocytic leukemia (B-CLL) and in 30 healthy subjects. As compared with controls, B-CLL patients had increased absolute numbers of phenotypically activated, HLA-DR+ CD4+ and CD8+ cells and T suppressor/effector (CD11b+CD8+) cells. When patients in Rai stages II through IV (n = 11) were compared with cases in Rai stages O through I (n = 12), the former group of patients had higher numbers of activated CD4+ and CD8+ T cells and decreased levels of suppressor/effector T cells. The absolute numbers of T suppressor/inducer (CD45R+CD4+) cells were elevated in patients with stage O through I disease but within normal range in stage II through IV leukemia. We further showed that the absolute numbers of NK-like (CD16+) cells and their activated counterparts (DR+CD16+) are elevated in B-CLL patients as compared with healthy subjects. The comparison of relative T and NK subsets in the blood of patients and controls showed that the proportions of CD4+, CD8+, and CD16+ cells expressing the activation marker HLA-DR were increased in B-CLL. Furthermore, the percentage of T-suppressor/inducer (CD45R+) cells within the CD4+ population was decreased in the patients. The proportion of T- suppressor/effector (CD11b+) cells within the CD8+ subset was reduced in subjects with stage II-IV disease only. When stimulated in vitro with the T-cell-dependent inducer TPA, B-CLL cells from patients in Rai stages II through IV secreted larger amounts of IgM as compared with cells from stage O through I patients. A positive correlation was observed between the degree of phenotypic activation of CD4+ T-helper cells and their functional capacity to augment IgM secretion by autologous B-CLL cells. Our findings indicate a tumor cell-directed regulatory role of T cells (and possibly NK cells as well) in B-CLL. Furthermore, monitoring of phenotypically activated and functional T- cell subsets may be helpful in the prediction of disease progression and timing of therapy in B-CLL.     

梅毒与梅毒合并病毒性肝炎患者外周血T淋巴细胞亚群变化*

目的 调查梅毒及其合并病毒性肝炎患者外周血T淋巴细胞亚群的变化。方法 2016年1月～2020年6月我院收治的93例感染苍白螺旋体(TP)梅毒患者中,单纯梅毒感染61例,TP合并CHB患者21例和TP合并CHC患者11例,另选择健康体检者84例。使用流式细胞仪检测外周血T淋巴细胞亚群。结果 梅毒患者外周血CD3⁺、CD4⁺、CD4⁺CD45RO⁺和CD8⁺CD45RA⁺细胞百分比及CD4⁺/CD8⁺细胞比值分别为(52.2±8.5)%、(40.3±5.7)%、(18.1±3.9)%、(12.4±3.7)%和(1.2±0.3),均显著低于健康人[分别为(69.1±7.6)%、(50.7±6.9)%、(20.6±4.7)%、(16.2±4.3)%和(1.9±0.5),P＜0.05],而外周血CD8⁺、CD4⁺CD45RA⁺和CD8⁺CD45RO⁺细胞百分比显著高于健康人[分别为(32.4±7.3)%、(24.7±6.5)%和(8.7±1.5)%对(26.2±5.4)%、(21.8±6.2)%和(5.4±1.1)%,P＜0.05];三组外周血CD8⁺、CD4⁺CD45RA⁺、CD4⁺CD45RO⁺、CD8⁺CD45RA⁺和CD8⁺CD45RO⁺细胞百分比及CD4⁺/CD8⁺细胞比值比较,差异有统计学意义(P＜0.05),TP合并CHB组和TP合并CHC组患者外周血CD8⁺、CD4⁺CD45RA⁺和CD8⁺CD45RO⁺细胞百分比均显著高于TP组(P＜0.05),而TP合并CHB组和TP合并CHC组患者外周血CD4⁺/CD8⁺比值、CD4⁺CD45RO⁺和CD8⁺CD45RA⁺细胞百分比显著低于TP组(P＜0.05),TP合并CHB组与TP合并CHC组患者外周血CD8⁺、CD4⁺CD45RA⁺、CD4⁺CD45RO⁺、CD8⁺CD45RA⁺和CD8⁺CD45RO⁺细胞百分比及CD4⁺/CD8⁺细胞比值比较均无统计学差异(P＞0.05)。结论 梅毒患者存在显著的外周血淋巴细胞亚群变化,合并CHB或合并CHC患者细胞免疫功能变化更明显,其临床意义值得进一步探讨。     

Reduction of CD45RA isoform expression and decrease in CD4 and CD8 receptor density in lymphocytes of patients with primary biliary cirrhosis

BACKGROUND: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. METHODS: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing 'naive' (CD45RA+) and 'memory' (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. RESULTS: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD19+ cells and NK lymphocytes; 2) a reduction in the percentage of 'naive' CD4+ but normal proportion of 'naive' CD8+ as well as CD4+ and CD8+ 'memory' cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of 'naive' and 'memory' T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. CONCLUSIONS: It is concluded that the reduction in number of 'suppressor-inducer-like 'naive' CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.     

A comparison of the expression of lymphocyte activation markers in blood, bronchial biopsies and bronchoalveolar lavage: evidence for an enrichment of activated T lymphocytes in the bronchoalveolar space.

In this study healthy never-smoking subjects (n = 18) were recruited from a population study. Bronchoalveolar lavage (BAL), blood lymphocytes and bronchial biopsies, analysed both in the epithelium and lamina propria, were stained for T and B lymphocytes, natural killer (NK) cells and different subpopulations of T lymphocytes. In BAL, significantly higher proportions of T lymphocytes (CD3), T lymphocyte activation markers; HLA-DR, CD26+, CD49a+, CD54+ and CD69+, helper T (CD3+4+) and memory helper T lymphocytes (CD4+45RO+29+) and memory T lymphocytes (CD3+45RO+) were found, compared to blood. However, the proportion of IL-2 receptor-positive T lymphocytes (CD25+) was lower in BAL than in blood. A previously described higher ratio of CD3+4+/CD3+8+ in BAL than in blood (3.4 vs 1.7; P = 0.001) was confirmed. In bronchial biopsies, we found significantly higher numbers of CD8+ cell profiles per mm2 in the epithelial compared to the lamina propria compartment. We conclude that healthy never-smoking men have higher levels of activated memory T lymphocytes in BAL than in blood, and that the T-cell subpopulations differ in the epithelial compared to the lamina propria compartment in the bronchial mucosa and these compartments should be analysed separately. It is reasonable to think that there is a gradient from blood to the airway lumen where T cells are recruited from blood to take part in the defense towards damaging agents.     

Analysis of bone marrow and peripheral blood immunoregulatory lymphocytes in patients with myelodysplastic syndrome

The cell surface phenotype of immunoregulatory lymphocytes in bone marrow (BM) and peripheral blood (PB) in myelodysplastic syndrome (MDS), a stem cell disorder, was analyzed. Mononuclear cells from 25 patients with refractory anemia (RA) and nine with RA with an excess of blasts (RAEB) were characterized by two-color flow cytometry using various monoclonal antibodies. No significant change of CD3+, CD4+, and CD8+ cells in PB, but a decrease of the percent of positive cells for CD8+ among the total lymphocyte (%CD8+ +) was noticed in RA patients. On the other hand, in BM of RA patients, a decrease in the number of CD4+cells, but not CD8+ +cells, was noted. In RAEB patients, the absolute numbers of CD3+, CD4+, CD8+, and CD8+ +cells in BM were decreased; however, the ratio of these lymphocytes was not changed. No change was observed among the CD4 + subsets in PB of RA or RAEB patients. In BM, a decrease in percentage of CD4+ CD45RA+ (% CD4+ CD45RA+; naive cell) and increases in CD4+ CD45RO+ (% CD4+ CD45RO+; memory cell) and CD4+ CD29+ (%CD4+ CD29+; helper/inducer) among CD4+ cells were found in both RA and RAEB patients. Analysis of the CD8+ + subset showed an increased number of CD8+ + CD11a+ cells (activated CTL) in both BM and PB of RA patients, but not of RAEB patients. Furthermore, increments in CD56+ and CD16+ cells among CD3- cells (natural killer; NK cells) were seen in RA patients but not in RAEB patients. It remains unclear whether lymphocytes in MDS patients were involved in the abnormal (MDS) clones, but our results regarding the increments of CD8+ + CD11a+ and NK cells in RA patients suggest that the mechanism of immune surveillance against the abnormal MDS clones was activated in these RA patients, but not in RAEB patients. Further investigation is required to clarify the functions of these immunoregulatory lymphocytes in MDS patients.     

Lymphocyte subset reconstitution after HLA-identical placental blood transplantation (PBT) or PBT plus bone marrow transplantation (BMT) in three children with beta-thalassemia major

The kinetics of circulating lymphoid cells were evaluated in three children suffering from beta-thalassemia major after HLA-identical sibling placental blood transplant (PBT) in one patient and placental blood plus bone marrow transplantation (BMT) in two patients. Recovery of the main lymphocyte subsets, as determined by phenotype analysis of circulating PBMCs, was complete within 2 months after transplant. NK (CD56+) cells were the first to appear in peripheral blood, followed by T (CD3+, CD2+, CD7+) and B (CD19+) cells. Of the T lymphocytes, the CD8+ were the first to reconstitute, but recovery of CD4+ cells was also rapid and within 6 months these T cells reached normal values. The expression of CD57 by NK or T cells was slightly delayed. The evaluation of RA and RO isoform expression of the CD45 molecule showed a prevalence of the CD45RA antigen with a ratio of 2-3:1. In the PBT only patient, T cells expressing the CD45RO antigen prevailed in the early post-transplant period. Severe or chronic GVHD was not observed. This experience demonstrates that reconstitution of lymphocyte subsets is successful in genetic hematological diseases after transplantation of HLA-identical placental blood or placental blood plus bone marrow from healthy or heterozygous siblings. Bone Marrow Transplantation (2000) 26, 743-747.     

Intracellular IFN-gamma expression by CD3+/CD8+ cell subset in B-CLL patients correlates with stage of the disease

Changes in the cytokine network may be responsible for malignant cell accumulation in B-cell chronic lymphocytic leukaemia (B-CLL). Among different cytokines of question interferon gamma (IFN-gamma) is indicated to prevent malignant cells from entering apoptosis. The aim of the study was to determine IFN-gamma production capacity of T-cell subsets and B lymphocytes in B-CLL patients in comparison with healthy individuals and during disease progression. Forty patients with newly diagnosed, untreated B-CLL and 20 healthy individuals were studied. The two- and three-colour flow cytometry techniques were used to detect intracellular cytokine expression. We detected statistically significantly higher percentage of both CD3+/CD4+/IFN-gamma+ and CD3+/CD8+/IFN-gamma+ in patients than in controls (P < 0.001 in both cases). Moreover the percentage of CD3+/CD8+/IFN-gamma+ cells correlated with stage of the disease (R = 0.39, P = 0.01) and parameters of disease progression like lymphocyte count and total tumour mass score (R = 0.33, P = 0.03 and R = 0.31, P = 0.04, respectively). By contrast, the percentage of CD19+/IFN-gamma+ cells in B-CLL group was lower than in controls (P < 0.01). These findings indicate that T-cell populations rather than malignant B cells are the source of IFN-gamma in B-CLL patients. The subset of CD3+/CD8+ cells expressing IFN-gamma seems to play a special role in the disease progression and more precise investigation should elucidate its role as a prognostic marker in B-CLL and a target for therapeutic strategies.     

Two-color immunofluorescence and flow cytometric analysis of lamina propria lymphocyte subsets in ulcerative colitis and Crohn's Disease

By using two-color immunofluorescence with fluorescein isothiocyanate (FITC) and phycoerythrin (PE)-labelled monoclonal antibodies and multiparameter flow cytometry, we investigated lamina propria lymphocyte subsets of patients with ulcerative colitis (UC) and Crohn's disease (CD). Leu-3/Leu-2 (CD4/CD8) ratio of lamina propria lymphocytes (LPL) of CD (mean±sd: 1.9±0.8,P<0.01) was significantly decreased compared with controls (3.3±1.1), because of an increased number of CD8+lymphocytes. The majority of lamina propria CD4+cells were CD4+, Leu-8-and CD4+, CD45R-both in controls and IBD tissue. Many lamina propria T lymphocytes were activated, expressing HLA-DR antigen not only in IBD but also in controls. NK cells defined by CD16 and CD 56 (3.0±1.4%,P<0.01) were significantly decreased in patients with UC compared with controls (6.5±3.0%). A low proportion of B cells in the intestinal mucosa expressed Leu-8 antigen and CD23 antigen. The proportion of activated B cells of LPL was high in IBD mucosa as well as normal mucosa. These findings suggest that local activation of B cells leads to the loss of the expression of Leu-8 antigen and CD23.     

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.     

Recent thymic emigrants,T regulatory cells,and BAFF level in children with X-linked agammaglobulinaemia in association with chronic respiratory disease

Background

X-linked agammaglobulinaemia (XLA) is a genetic disorder affecting B cell maturation, which is characterised by a low number of B cells, agammaglobulinaemia and increased susceptibility to a variety of bacterial infections. This study was performed to assess T cell subpopulations in a group of children with XLA in association with chronic respiratory disease (CRD).

Transfusion-Related Immunomodulation in Chinese Children with Thalassaemia

Background and objectives: Multiple transfusions can induce immunomodulation. This study was carried out to investigate the immunological status of 50 transfusion-dependent children with β-thalassaemia, taking into account that lymphocyte characteristics are affected by sex, age and race. We paid particular attention to the influence of transfusion and serum ferritin on the lymphocyte subsets which may be affected by the exposure to foreign antigens. Materials and methods: By multicolour immunofluorescent analysis using flow cytometry, we determined lymphocyte characteristics with regard to major subsets (T lymphocytes, B lymphocytes and NK cells), activation (membrane IL-2 receptor CD25, HLA-D) and memory/naive T cells (CD45RO/CD45RA). Data from 51 age- and sex-balanced children served as controls. Results: The normal Chinese children had higher NK levels than the β-thalassaemia children. The levels of CD25 and HLA-D indicated a broad-based increase in activation status. Memory T cells were also increased when compared with their normal counterparts. We found additional and more marked alterations in the lymphocyte subsets of those who had received over 100 transfusions. While levels of NK cells were inversely correlated with the number of transfusions, CD25+ cells increased with transfusions. Conclusion: Many multitransfused β-thalassaemia children have altered levels of lymphocyte subsets compared with normals. What remains to be investigated is the long-term consequence of possessing low NK and non-MHC-restricted T cells (CD3+CD56+CD16+) and a high activation status in terms of resistance of infections and development of malignancy.     

The effect of hemodialysis on the virgin CD45RA+, CD45RO- and memory CD45RO+, CD45RA- lymphocyte count in patients with chronic renal failure

The hallmark of immunological memory is a quick and effective response to a repeated antigen exposure. Virgin lymphocytes, with their surface receptors CD45RA+, CD45RO- are produced in primary lymphatic organs, then migrating to secondary lymphatic structures. Memory lymphocytes CD45RO+, CD45RA- produced in these organs migrate to non-lymphatic organs--a possible location of inflammatory process, thus enabling the immunological system to eliminate effectively the same antigen, when repeatedly present. The aim of the study was 1) to test the influence of hemodialysis on the number of virgin lymphocytes and/or memory lymphocytes; 2) whether such impact (if any) depends on the type of dialysis membrane used (cuprophan or polysulphon), 3) if the effect is different in patients with or without diabetes. Overall number of virgin T helper lymphocytes CD45RA+CD4+ was significantly lower in patients with end-stage renal disease, while the number of total CD45RO+, CD45RA- memory lymphocytes was significantly greater among patients with diabetic nephropathy, compared to normal control subjects. After 15 minutes of hemodialysis, number of virgin lymphocytes CD45RA+, CD45RO- (p < 0.001, p < 0.01) and their subclasses, as well as memory lymphocytes CD45RO+, CD45RA- were significantly decreased. After 15 minutes of hemodialysis with polysulphon membrane, the decrease in T virgin cytotoxic, B virgin CD45RA+CD4-, T memory cytotoxic as well as B memory CD45RO+CD4- lymphocytes was significantly lower, when compared with cuprophan membrane (p < 0.02). Among patients treated with cuprophan hemodialysis, the decrease of T helper memory CD45RO+CD4+ lymphocytes was significantly lower in patients with diabetic nephropathy, than in non-diabetic patients. CONCLUSIONS: In all patients with end-stage renal disease, the impact of hemodialysis on the number of memory lymphocytes CD45RO+, CD45RA-, as well as virgin lymphocytes CD45RA+, CD45RO- was shown, but the effect was less profound during hemodialysis with polysulphon membrane, compared to cuprophan. The presence of diabetic nephropathy effects the hemodialysis-induced changes in the number of T memory helper CD45RO+ CD45RO+CD4+ lymphocytes, with no impact on other subclasses of the examined cells.     

Age- and sex-related changes of the lymphocyte subsets in healthy individuals: an analysis by two-dimensional flow cytometry

The relative and absolute numbers of the peripheral blood lymphocyte (PBL) subpopulations from 156 healthy men and women of different ages (20-99 years old) were studied by the use of monoclonal antibodies (MoAbs) and two-dimensional flow cytometry. The percentage of pan-T MoAb-positive cells decreased with age, which was attributable to a relative decline in the CD8+ suppressor/cytotoxic T cells, more precisely in the CD8+ CD11- cytotoxic T cells. Those of CD4+ Leu-8- helper T cells, CD3+ HLA-DR+-activated T cells, and natural killer subsets (Leu-7+, CD16+, Leu-7+ CD16+ or Leu-7+ CD16-) increased with age. The absolute numbers of most of the lymphocyte subsets examined declined with age except that those of natural killer cell subsets and helper T cells remained unchanged. It should be noted that the PBL subsets differed markedly according to age and sex, the changes being more evident among women.     

Decreased Blood Natural Killer Cell Activity and Immunoglobulin Synthesis in vitro in Aplastic Anemia

Abstract. Natural killer (NK) cell numbers and T lymphocyte subpopulations in peripheral blood were evaluated in six patients with aplastic anemia (AA). The immunophenotyping results were correlated to in vitro tests of NK cell cytotoxicity against K562 cells and of immunoglobulin (Ig) production after pokeweed mitogen (PWM) stimulation. A significant decrease was found both in the percentage of Leu 11 positive cells and in NK cell activity as compared to age- and sex-matched healthy controls. The decrease in NK cell activity could not be entirely compensated by an increase in effector/target cell ratios, thus suggesting not only a quantitative but also a functional defect in NK cells of the AA patients. Three of four AA patients tested showed no major increase of Ig production after PWM stimulation. All these three patients also had fewer “functional T helper” cells (Leu3+/Leu8^–) and increased numbers of T suppressor/cytotoxic cells (Leu2+) when compared to controls. No significant differences in numbers of B lymphocytes (B1+) could be found. Our findings suggest a possible linkeage between quantitative and qualitative abnormalities in lymphocyte subsets in aplastic anemia. However, no evidence was found to support the hypothesis of increased NK cell activation behind the hemopoietic depression in this disease.     

支气管哮喘患者记忆性T淋巴细胞对B淋巴细胞产生IgE作用的研究

目的 探讨记忆性（ＣＤ４＾＋ＣＤ４５ＲＯ＾＋）Ｔ淋巴细胞在支气管哮喘的发病中的作用。方法 分别分离出支气管哮喘病人及健康对照的ＣＤ４＾＋ＣＤ４５ＲＯ＾＋Ｔ淋巴细胞亚群,并将其与各自的Ｂ淋巴细胞共同培养,设定刺激组（美洲商陆有丝分裂原）及非刺激组,测定培养上清液中ＩｇＥ的含量。结果 哮喘病人自然状态的ＣＤ４＾＋ＣＤ４５ＲＯ＾＋Ｔ淋巴细胞对Ｂ淋巴细胞产生ＩｇＥ有正向促进作用,但有接受美洲商陆有丝分裂原     

脾栓塞对肝硬化患者外周血T淋巴细胞亚群的影响

目的 :研究部分脾栓塞治疗脾功能亢进对肝硬化患者T淋巴细胞亚群的影响。方法 :57例肝硬化并脾功能亢进患者 ,32例采用部分脾栓塞治疗 ,2 5例采用脾全切治疗 ,1 5例正常人作为对照 ,比较两组治疗前后外周血T淋巴细胞亚群的变化。结果 :肝硬化患者外周血T淋巴细胞 (CD3+ )、T辅助 /诱导淋巴细胞亚群 (CD4+ )、T辅助淋巴细胞 /T抑制淋巴细胞亚群 (CD4+ /CD8+ )明显低于正常人 (P <0 .0 1 ) ;脾栓塞组治疗前后CD3+ 、CD4+ 、CD8+ 、CD4+ /CD8+ 无明显差异 (P >0 .0 5) ;脾全切组治疗后CD3+ 、CD4+ 、CD4+ /CD8+ 均较治疗前及部分脾栓塞组治疗后明显降低 (P <0 .0 1 )。结论 :肝硬化患者外周血CD3+ 、CD4+ 、CD4+ /CD8+ 降低 ,部分脾栓塞治疗脾功能亢进 ,对肝硬化患者外周血T淋巴细胞亚群无明显影响 ,显著优于脾全切治疗     

Activation of T cell subsets in the peripheral blood of patients with Sj?gren's syndrome. Multicolor flow cytometric analysis.

Using 3-color flow cytometry, we determined the proportions of activated T cells (DR+), including CD4+ cells, CD8+ cells, and their subsets, in the peripheral blood of 17 patients with Sj?gren's syndrome (SS). Activated T cells were significantly increased in CD4+ cells, CD8+ cells, and T suppressor inducer (CD4+, Leu-8+), T helper (CD4+, Leu-8-), and T cytotoxic (CD8+, CD11-) subsets, but not the T suppressor/natural killer subset (CD8+, CD11+), in patients with SS as compared with the controls. Furthermore, the proportions of activated T cells in the CD4+, Leu-8- subset, the CD8+ subset, or the CD8+, CD11- subset showed a positive correlation with serum gamma globulin levels in the SS patients. Our findings suggest that a certain immunoregulatory balance between T helper and T suppressor activities is maintained in SS patients, although this balance seems to occur at highly activated levels, and that quantitative changes of some lymphocyte subsets are important factors in maintaining this balance. We discuss the possibility that CD4+, Leu-8+ cells recirculate into peripheral lymph nodes, while CD4+, Leu-8- cells migrate into inflammatory tissues such as salivary glands, since the Leu-8 antigen is reported to be a homing receptor in peripheral lymph nodes. This process might be accelerated in SS, and each T cell subset may further participate in immunologic activation in the lymph nodes or target tissues.     

慢性乙型肝炎患者外周血淋巴细胞亚群与病程相关性的研究

目的对慢性乙型肝炎轻中度、重度和肝硬化患者外周血淋巴细胞亚群的百分比和绝对细胞数进行观察,探讨慢性乙型肝炎患者外周血淋巴细胞亚群的变化与病程的关系.方法采集88例慢性乙型肝炎患者柠檬酸钠新鲜抗凝血,经流式细胞仪进行免疫分型检测.结果慢性乙型肝炎重度患者的CD3+CD4+细胞百分比显著低于轻中度患者(P＜0.05),肝硬化患者的CD3+和CD3+CD8+细胞百分比显著低于轻中度患者(P＜0.01).肝硬化患者CD3CD19+细胞百分比显著高于重度和轻中度患者(P＜0.01).CD4/CD8比例在慢性乙型肝炎轻中度、重度和肝硬化患者间无显著差异.肝硬化和重度患者淋巴细胞、CD3+、CD3+CD4+、CD3+CD8+细胞的绝对细胞数均显著低于轻中度患者(P＜0.01),且肝硬化患者CD3-CD16+56+细胞的绝对细胞数显著低于轻中度患者(P＜0.05).肝硬化患者与轻中度患者的DNA载量分布差异有显著性(P＜0.01),其高水平病毒载量的患者比例高于轻中度患者.结论慢性乙型肝炎轻中度发展为重度和肝硬化的过程中,外周血淋巴细胞亚群绝对细胞数随病情的进展显著减少,主要表现为CD3+CD4+和CD3+CD8+的T淋巴细胞亚群的百分比进行性降低.     

Association of natural killer cell immune recovery with a graft-versus-leukemia effect independent of graft-versus-host disease following allogeneic bone marrow transplantation

 There is good evidence that T lymphocytes play an important role in the graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT) for hematologic malignancies. However, the role of natural killer (NK) cells in GVL is less clear. To further investigate a possible association of NK cells with GVL we studied 15 patients undergoing BMT for chronic myeloid leukemia (CML), correlating T-cell (CD4+ and CD8+) and NK-cell (CD16+56+) recovery with relapse and graft-versus-host disease (GVHD). Patients were studied on three occasions up to 9 months after BMT, for lymphocyte surface phenotype and for spontaneous and IL-2-stimulated (LAK cell) cytotoxic function. Circulating CD8+ and NK but not CD4+ cell numbers were significantly lower in five patients who relapsed compared with those remaining in remission after BMT (mean 0.03 vs 0.32×10⁹/l, p=0.002 for CD8+ cells; mean 0.03 vs 0.11×10⁹/l, p=0.002 for NK cells). There was no correlation of CD4+, CD8+, or NK cell numbers and development of grade-II or more acute GVHD. Spontaneous NK cytotoxic function rose to within the normal range in the first month after BMT. LAK function remained low during the study period. These results link NK cell recovery more closely with a GVL than with a GVH effect. Received: 1 May 1996/Accepted: 19 September 1996