Variable lymphocyte receptors in hagfish

A previously uncharacterized type of variable lymphocyte receptors (VLR) was identified recently in the Sea lamprey. This jawless vertebrate generates an extensive VLR repertoire through differential insertion of neighboring diverse leucine-rich repeat (LRR) cassettes into an incomplete germ-line VLR gene. We report here VLR homologs from two additional lamprey species and the presence of two types of VLR genes in hagfish, the only other order of contemporary jawless vertebrates. As in the Sea lamprey, the incomplete hagfish germ-line VLR-A and -B genes are modified in lymphocyte-like cells to generate highly diverse repertoires of VLR-A and -B proteins via a presently undetermined mechanism. This jawless-fish mode of VLR diversification starkly contrasts with the rearrangement of Ig V(D)J gene segments used by all jawed vertebrates to produce diverse repertoires of T and B lymphocyte antigen receptors. The development of two very different strategies for receptor diversification at the dawn of vertebrate evolution approximately 500 million years ago attests to the fitness value of a lymphocyte-based system of anticipatory immunity.     

Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma

Because there is controversy regarding whether subsets of peripheral blood lymphocytes (PBLs) are part of the malignant clone in patients with multiple myeloma, we studied this question by immunoglobulin and T cell receptor gene analysis. Southern blot analysis with antibody probes demonstrated clonal immunoglobulin gene rearrangements in PBLs of seven of nine patients that were identical to those seen in their marrow plasma cells. Circulating plasma cells were not detected in any of these patients. In contrast, no patient demonstrated clonally rearranged T cell receptor genes. In one sequentially studied patient, PBLs obtained at diagnosis when he had stage I (Durie-Salmon) contained only germline DNA, while analysis of PBLs at relapse (stage III) revealed a clonally rearranged band. These data confirm the notion that circulating lymphocytes in patients with myeloma are part of the malignant clone and, furthermore, these malignant cells are of B cell rather than T cell lineage.     

T lymphocyte colony assay in hemophiliacs

Unexplained lymphadenopathy, with or without accompanying symptoms, known as the "lymphadenopathy syndrome," has been recognized in groups at risk for acquired immune deficiency syndrome (AIDS), namely, homosexuals and hemophiliacs. To date, however, no test has been defined that discriminates between asymptomatic individuals and those with adenopathy in these high-risk groups. The T colony assay, which measures T lymphocyte growth in soft agar and which allows selective T cell proliferation with minimal cell-cell contact, was evaluated in asymptomatic hemophiliacs. Significantly lower mean colony counts were found in eight hemophiliacs with adenopathy (HA), 763 +/- 348 (+/- SEM), than in 16 healthy hemophiliacs (HH) 3,044 +/- 661 (P less than .005), or than in 24 heterosexual control subjects, 3,964 +/- 395 (P less than .005). The in vitro addition of exogenous interleukin-2 (IL- 2) restored normal colony growth in the HA population. These results indicate that the T colony assay can detect abnormal cell-mediated immunity among hemophiliacs and specifically discriminates between asymptomatic hemophiliacs (HH) and those with adenopathy (HA). In addition, IL-2 may be of potential benefit in improving T cell defects in AIDS or the "lymphadenopathy syndrome"; however, this remains to be proven.     

Circulating lymphocyte subpopulations in Crohn's disease

Circulating lymphocytes were enumerated in 28 patients with Crohn's disease and in 12 patients with other diseases by rosetting and by immunofluorescent staining using monoclonal antibodies for T-cell surface phenotypic markers [OKT3 (mature), OKT4 (helper), and OKT8 (suppressor/cytotoxic)] or polyvalent antisera for surface immunoglobulins (B cells). Total lymphocyte counts were reduced only in those with non-steroid-treated active Crohn's disease. Circulating monocyte counts, proportions of peripheral T and B cells, and percentages and absolute numbers of mature, helper, and suppressor T-cell subclasses in Crohn's disease were not significantly different than in the controls. Helper to suppressor T-cell ratios were comparable in all subjects, varying directly with numbers of helper T cells (p less than 0.05). Individual ratios of helper to suppressor T cells did not correlate with disease activity or location, the use of steroids, serum albumin, or total lymphocyte or monocyte counts. This study provides no evidence for underlying abnormalities of circulating lymphocyte subpopulations in Crohn's disease when compared to subjects with other illnesses. The characterization of lymphocyte subclasses in affected tissues is an important area of continuing investigation.     

Canine lymphocyte subpopulations

Ten to 23% of cells in blood, lymph node and bone marrow from normal dogs formed rosettes with human erythrocytes, and 12-27% formed rosettes with erythrocyte-antibody-complement (EAC) complexes. In contrast, only 3% of thymocytes, and 1% of thoracic duct cells formed rosettes with human erythroyctes, and 0 and 15% respectively formed EAC rosettes. When peripheral blood mononuclear cells were separated by rosette sedimentation into populations depleted of, or enriched for, cells forming rosettes with human erythrocytes (H-RFC), the population depleted of H-RFC responded more vigorously to alloantigens in mixed leukocyte culture (MLC) (P < 0.01) and to the mitogens phytohemagglutinin (PHA) (P = 0.01) and concanavalin A (P = 0.01) than did the population enriched for H-RFC. Passage of peripheral blood mononuclear cells over nylon wool columns produced a nonadherent population depleted of H-RFC, EAC rosette-forming cells and cells binding surface immunoglobulin (SIg), while the adherent population was enriched for each of these markers. In 3 dogs 36%, 44% and 64% of adherent cells that formed rosettes with human erythrocytes also possessed SIg, suggesting that canine B cells form rosettes with human red cells. The nonadherent population showed a more vigorous response to alloantigens in MLC (P < 0.01) and to PHA (P < 0.05) than the adherent population, and also stimulated the growth of autologous erythroid colonies better than the adherent population (P = 0.02). A T cell rich population can thus be obtained from canine peripheral blood, but no specific marker for T cells has been identified. Specifically, the capacity to form rosettes with human red cells is not a marker for the canine T cell.     

T lymphocyte subpopulations in myelodysplastic syndromes

T cell subpopulations, defined by monoclonal antibodies (OKT3, OKT4 and OKT8), were assessed on 13 patients with myelodysplasia (MDS). The percentage and numbers of OKT3- and OKT4-positive lymphocytes were significantly lower (p less than 0.025) than in normal controls, whereas those of OKT8 were not. In the group of patients with refractory anemia with excess of blasts (RAEB) and in those with chronic myelomonocytic leukemia, the percentage and absolute numbers of OKT8 lymphocytes were significantly lower (p less than 0.025) than in patients with refractory anemia or with primary acquired sideroblastic anemia, while those of OKT3 and OKT4 did not differ significantly. Quantitative impairment of T cell subpopulations may be part of the myelodysplastic situation as a result of the dyslymphopoiesis, according to the hypothesis that MDS originate from pluripotent stem cells. The decrease of OKT8 in RAEB and chronic myelomonocytic leukemia could be related to the previously shown insufficient erythropoietic activity in these patients.     

Age-related variation in lymphocyte subpopulations.

Peripheral blood lymphocytes are heterogeneous and can be divided into subpopulations based on cell surface markers. Lymphocytes from 101 normal individuals of all ages were tested for their ability to form spontaneous rosettes with sheep erythrocytes (T cells) and for surface immunoglobulins (B cells). Cord bloods of newborn infants and bloods from children (age 1-10 years) showed greater numbers of total lymphocytes, total T cells and unmarked cells than a control group of 50 individuals from age 11-60 years. In 22 normal elderly individuals (age 61-98 years), total lymphocytes and total T and B cells were not decreased. These data suggest that the depression of cellular immune response described in elderly populations may be related to a dysfunction in a segment of T cells or an aberration in the complex interaction among T cells, B cells and macrophages.     

Human lymphocyte antigens in hypertrophic cardiomyopathy

An increasing number of genetic studies in hypertrophic cardiomyopathy challenge conventional views on inheritance and suggest genetic heterogeneity or non-genetic disease. We have found changes in relative risk for some antigens with significantly increased frequency of HLA antigen DR4 in this condition. These findings are consistent with there being a genetic component in susceptibility to hypertrophic cardiomyopathy. No evidence was found for HLA linkage using either sib pair analysis or lod scores. This suggests that hypertrophic cardiomyopathy does not have a disease susceptibility gene related to the HLA region on the short arm of chromosome number six. Population HLA associations with hypertrophic cardiomyopathy must thus be explained by other influences of the genetic background on disease susceptibility.     

T lymphocyte abnormalities in disseminated histoplasmosis

Disseminated histoplasmosis is associated with depression of T cell-mediated immunity and in some cases anergy. In this report, two patients with disseminated disease are described. Both had a depression of T cell-mediated immunity as well as other abnormalities of immune response. In one, a patient with relapse, a marked depression in the ratio of T helper to T suppressor cells was noted. Neither patient had any predisposing condition known to be associated with disseminated disease.     

Altered lymphocyte reactivity in rheumatoid arthritis

Blastogenic transformation of peripheral lymphocytes with phytohemagglutinin (PHA), conconavalin A (Con A), and pokeweed mitogen (PWM) was studied in 29 patients with rheumatoid arthritis (RA). The PHA response was depressed in a subgroup of RA patients with erosive disease. The Con A response was also depressed and paralleled the PHA response. The PWM response was not depressed. These results lend support to the hypothesis of a functional defect of cellular immunity in RA. It was shown that lymphocyte responsiveness to a single mitogen concentration is not an adequate assessment of the overall responsiveness of the lymphocytes tested.     

B lymphocyte dysfunctions in HIV infection

HIV establishes a chronic and latent infection that is not eliminated by the host immune defences. The virus induces extensive damage to the immune system, through virus-related and indirect pathogenic mechanisms. Both the cellular and the humoral arms of the immune system are unable to control the infection, which ultimately results in severe exhaustion of several lymphocyte functions and increased susceptibility to secondary and opportunistic infections. A striking pathological feature induced by the persistent viral replication is the aberrant activation of cells of the immune system. Among these cells, B lymphocytes are severely damaged and show signs of phenotypic and functional alterations. In parallel to the polyclonal B cell activation and hypergammaglobulinemia, B cells from patients show impaired reactivity to immunisation and in vitro activation signals. In addition, B lymphocytes from HIV-infected subjects are primed for apoptosis. The role of protective humoral immunity in the control and clinical progression of HIV infection is still much debated and controversial. The aim of the present review is to discuss the mechanisms involved in the loss of B cell functions during HIV infection. In particular, we discuss the role that T and B cell immune activation plays for B cell polyclonal activation and loss of memory B lymphocytes. The current knowledge on B cell damage is also discussed in the context of anti-HIV therapeutic treatment.     

Cinemicroscopic studies of lymphocyte behavior in semi-solid medium: the polyclonal origin of lymphocyte colonies

Time-lapse cinemicroscopy was used to observe the development of lymphocyte colonies in a phytohemagglutinin-dependent one-step, two-layer agar culture system. More than 1000 h of culture time were recorded in a total of 14 independent experiments. Blast formation and organization of lymphocytes into highly motile pairs and clusters occurred early in culture (0-3 days). An increase in thymidine uptake also preceded the first detectable proliferation by 24 h. Mature lymphocyte colonies were found to be dynamic entities characterized by the continuous influx and egress of highly motile cells. Cell clusters and entire colonies were observed to locomote and on several occasions fuse to form larger structures. Macrophagelike cells located centrally within colonies appeared to play a major role in such behavior. Taken together these results conclusively demonstrate that, in the present system, lymphocyte colonies are the product of a complex pattern of cell interaction, proliferation, and cell motility and, as such, are polyclonal in origin.     

Neutrophil to lymphocyte and platelet to lymphocyte ratio in patients with dipper versus non-dipper hypertension

Background: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are associated with worse outcome in various diseases. Non-dipping blood pressure pattern is associated with higher cardiovascular mortality. The aim of this study was to explore the association between NLR and PLR in patients with dipper versus non-dipper hypertension.

Methods: The study included 166 patients with hypertension. Eighty-three patients (40 male, mean age: 49.1?±?10.5 years) had dipper hypertension, while 83 patients (41 male, mean age: 52.3?±?12.7 years) had non-dipper hypertension.

Results: Baseline demographic characteristics were similar in both groups. Patients with non-dipper hypertension had significantly higher NLR compared to dipper hypertension (2.3?±?0.9 versus 1.8?±?0.5, p?p?=?0.001). In univariate analysis, hyperlipidemia, smoking, presence of diabetes, PLR more than 107 and NLR more than 1.89 were among predictors of dipper and non-dipper status. In logistic regression analyses, only hyperlipidemia (odds ratio: 2.96, CI: 1.22–7.13) and PLR more than 107 (odds ratio: 2.62, CI: 1.13–6.06) were independent predictors of dipper and non-dipper status. A PLR of 107 or higher predicted non-dipper status with a sensitivity of 66.3% and specificity of 68.7%.

Conclusion: We demonstrated that patients with non-dipper hypertension had significantly higher NLR and PLR compared to dipper hypertension, which has not been reported previously. Moreover PLR more than 107 but not NLR was independent predictor of non-dipper status.     

肺腺癌患者中性粒细胞-淋巴细胞比率和血小板-淋巴细胞比率的临床价值

<正>肺癌在世界上是发病率最高的肿瘤,其死亡率也居世界上癌症患者死亡的首位[1],而所有的肺癌中,肺腺癌所占比重最高,并且发病率逐渐升高[2]。尽管近些年来关于肺腺癌早期诊断的分子标志物不断增多,但是只有极少数真正实现了临床应用,多是因为这些靶标缺少充足的临床证明,以及难以标准化检测[3]。因此,对于患者的常规检查结果进行分析是很有意义的。近年来研究发现,中性粒细胞与淋巴细胞比率(neutrophil to lymphocyte ratio,NLR)以及血小板与淋巴细胞比率(platelet to lymphocyte ratio,PLR)与多种肿瘤的病理参数以及预后密切相关[4-6],因此,对NLR和PLR与肺癌之间的关系进行研究有重要意义。