Differential migration behavior and chemokine production by myeloid and plasmacytoid dendritic cells

The existence of dendritic cell (DC) subsets is firmly established, but their trafficking properties are still largely unknown. We have indicated that myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs) isolated from human blood differ widely in the capacity to migrate to chemotactic stimuli. The pattern of chemokine receptors expressed ex vivo by both subsets is similar, but P-DCs display, compared with M-DCs, higher levels of CC chemokine receptor (CCR)5, CCR7, and CXCR3. Intriguingly, most chemokine receptors of P-DCs, in particular those specific for inflammatory chemokines and classical chemotactic agonists, are not functional in circulating cells. Following maturation induced by cluster designation (CD)40 ligation, the receptors for inflammatory chemokines are downregulated and CCR7 on P-DCs becomes coupled to migration. The drastically impaired capacity of blood P-DCs to migrate in response to inflammatory chemotactic signals contrasts with the response to lymph node-homing chemokines, indicating a propensity to migrate to secondary lymphoid organs rather than to sites of inflammation. The distinct migration behavior of DC subsets is accompanied by a different profile of chemokine production. In contrast to the high production by M-DCs, the homeostatic CC chemokine ligand (CCL)17/ thymus- and activation-regulated chemokine (TARC) is not produced by PDCs in response to any stimulus tested and their production of CCL22/MDC is minimal, if any, compared with M-DCs. Thus, stimulated M-DCs, but not P-DCs, are able to produce high levels of chemokines recruiting T-helper 2 cells (Th2) and T-regulatory cells. Conversely, the proinflammatory chemokine CCL3/macrophage inflammatory protein (MIP)-1 is predominantly produced by P-DCs. Therefore, P-DCs appear to produce preferentially proinflammatory chemokines, but to respond selectively to homeostatic ones, whereas the reverse is true for M-DCs, highlighting not only the different migratory properties of these DC subsets, but also their capacity to recruit different cell types at inflammation sites.     

The effect of testosterone replacement treatment on immunological features of patients with Klinefelter's syndrome

Although the effects of androgen deficiency in the immune system have long been appreciated, little is known about the immunological features of patients with Klinefelter's syndrome (KS). On the other hand, interest in androgens as a possible treatment for some autoimmune diseases is growing. In the present study, some immunological parameters were evaluated in 26 patients with KS prior to androgen replacement treatment (ART) and the results were compared with those in 19 healthy control subjects. Patients were then treated with testosterone for 6 months and the pre- and post-treatment findings were compared. Serum levels of IgG, IgA, IgM, C3c and C4 were measured by nephelometry and lymphocyte subsets and CD4+/CD8+ ratios were examined by flow cytometry. IL-2 and IL-4 levels were measured by ELISA. Pretreatment levels of the serum IgA, IgG, IgM, IL-2 and IL-4 of the patients were higher than those of the controls and were all decreased significantly following ART. The pretreatment absolute numbers and percentages of CD3+, CD4+, CD19+ cells and CD4+/CD8+ ratios of patients with KS were higher than those of the controls and were all decreased with ART. Percentages of CD8+ cells were increased significantly, while C3 and C4 levels were both significantly decreased after ART. It is concluded that the lack of testosterone in patients with KS enhances cellular and humoral immunity and that ART may suppress this.     

Clonal anergy to staphylococcal enterotoxin B in vivo: selective effects on T cell subsets and lymphokines

Injection of bacterial superantigens such as staphylococcal enterotoxin B (SEB) in adult mice results in initial proliferation of SEB-responsive Vβ8⁺ T cells followed by induction of a state of non-responsiveness frequently referred to as clonal anergy. We show here that SEB-induced anergy involves selective changes in lymphokine production and that it affects CD4⁺ Vβ 8⁺ and CD8⁺ Vβ 8⁺ T cells in different fashions. Whereas both CD4⁺ Vβ 8⁺ and CD8⁺ Vβ 8⁺ cells from anergic mice exhibit strongly reduced proliferative capacity and interleukin(IL)-2 production upon restimulation with SEB either in vivo or in vitro the CD8⁺ subset from SEB-injected mice produces other lymphokines (such as interferon(IFN)-γ) at normal or slightly increased levels in response to SEB. Changes in the levels of production of IL-2 and IFN-γ protein correlated well with mRNA accumulation both in vivo and in vitro. Collectively these data suggest that superantigen-induced anergy involves selective changes in signal transduction and/or gene regulation in T lymphocytes.     

再生障碍性贫血患者细胞免疫指标的观察

采用酶免疫和放射免疫法分析了再生障碍性贫血(AA)患者外周血T淋巴细胞亚群、血清肿瘤坏死因子(TNF)、γ-干扰素(IFN-γ)和IL-2水平,以及患者外周血单个核细胞体外诱生的上述细胞因子水平。结果表明:患者CD4/CD8细胞比值降低或倒置(P<0.001),血清TNF和IFN-γ水平显著增高(P<0.01),外周血单个核细胞诱生的TNF、IFN-γ和IL-2水平均明显高于正常对照(P<0.01)。提示T淋巴细胞亚群比例失调和TNF、IFN-γ等造血负调控因子的过量分泌可能与AA的发病机制有关。     

Phenotypic analyses of mononuclear cells recovered from healthy and diseased human periodontal tissues

Mononuclear cells were recovered from the gingival tissues of normal individuals and from patients with periodontal disease. Lymphocyte phenotypic markers were identified by immunofluorescence after reaction with monoclonal antibodies to T-cell subset markers. The normal tissues exhibited T4/T8 ratios almost identical to those in the peripheral blood. The diseased tissue cell ratios were significantly reduced, in both the adult periodontitis and the juvenile periodontitis groups (P<0.01 andP<0.02, respectively), indicating alterations in the T-cell subset distribution in these tissues. Each diseased patient showed a much decreased T4/T8 ratio in the gingival lymphocytes when these were compared with the peripheral blood ratio from the same patient. The T4/T8 ratios of the more severe sites were significantly lower than those of the less severe sites in the same disease category. The decreases in subset ratios could be attributed to statistically significant reductions in T4⁺-lymphocyte recoveries relative to peripheral blood and also to slight relative increases in T8⁺ lymphocytes. A highly significant (P<0.001) correlation between the average probeable periodontal pocket depth and the T4/T8 ratio of each disease category was demonstrated. The relative recoveries of B cells from the various tissues did not differ between diseased and normal tissues. It is suggested that T-cell regulatory expression in gingival tissues is distinct from peripheral blood regulatory expression and that there is a local immunoregulatory imbalance in periodontal disease.     

Antibody to human immunodeficiency virus correlates with decreased T helper lymphocytes in asymptomatic individuals

To examine the relationship between human immunodeficiency virus (HIV) seropositivity and T lymphocyte subsets in a clinically well population, we assayed HIV antibody and analyzed T lymphocyte subsets in 30 people at increased risk for acquired immunodeficiency syndrome (AIDS) who were clinically well. Seventy-six percent of the HIV-seropositive individuals had abnormally low numbers of T helper lymphocytes, and HIV seropositivity was strongly correlated with an abnormally low number of T helper cells (p less than 0.00002). Among these clinically well subjects at increased risk for AIDS, HIV-sero-positive individuals had a significant decrease in mean T helper lymphocytes and mean T helper:T suppressor ratios as compared to those who were seronegative (483 cells/mm3 vs 915 cells/mm3, p less than 0.002; and 0.80 vs 1.7, p less than 0.002, respectively). Because of the strong correlation of HIV seropositivity and abnormally low numbers of T helper lymphocytes in this asymptomatic population, these findings suggest that asymptomatic seropositive individuals should be followed closely for development of AIDS-related disease and should be considered for future antiviral therapy when it becomes available.     

Impaired mononuclear-cell proliferation in patients with the acquired immune deficiency syndrome results from abnormalities of both T lymphocytes and adherent mononuclear cells

Peripheral blood mononuclear cells from patients with acquired immune deficiency syndrome proliferate poorly after stimulation with soluble mitogens. The present study was undertaken to assess the relative contributions of T lymphocytes and of plastic adherent mononuclear cells to the impaired mononuclear cell responses. We employed a four-step separation procedure including terminal depletion using a monocyte-specific monoclonal antibody (61D3) to derive populations of highly purified T cells from patients and from normal subjects. Highly purified T cells proliferated poorly in response to phytohemagglutinin and pokeweed mitogen. The addition of autologous adherent cells to highly purified T cells markedly improved mitogen-driven proliferation in all subjects; however, mononuclear cells from patients with AIDS responded less well than normals (P0.01) for both phytohemagglutinin and pokeweed. Allogeneic normal adherent cells fully restored both phytohemagglutinin and pokeweed responses in normal highly purified T cells. Adherent cells from patients were comparable to normal adherent cells in phytohemagglutinin-driven proliferation but performed significantly less well when pokeweed was used to stimulate normal highly purified T-cell responders (4308 cpm after coculture with patients' adherent cells vs 8244 cpm after coculture with allogeneic normal adherent cells;P=0.05). Similarly, when patient's highly purified T cells were stimulated with pokeweed mitogen, control adherent cells functioned substantially better than patient adherent cells (1198 cpm for allogeneic patient adherent cells vs 2324 cpm for normal adherent cells;P=0.05). Although the addition of normal adherent cells to patients' highly purified T cells significantly improved pokeweed mitogen responses, these values did not reach normal. Suppression by patients adherent cells was not demonstrated. Abnormal mitogen responses in acquired immunodeficiency appear to be primarily a result of an intrinsic T-lymphocyte disorder. This defect cannot be correctedin vitro by coculture with normal adherent cells. Adherent mononuclear cells from patients with acquired immunodeficiency supported phytohemagglutinin responses as well as normal adherent cells. However, patients' adherent cells showed decreased accessory function when pokeweed mitogen was employed to stimulate responder cells. These data suggest that abnormalities of adherent mononuclear cells are present in patients with acquired immunodeficiency and that this defect may contribute to the impaired mitogen responses in these patients. Pokeweed mitogen assays are particularly sensitive in demonstrating abnormal accessory-cell function.The opinions and assertions expressed herein are those of the authors and are not to be construed as official or as reflecting the views of the Navy Department or of the Naval Service at large.     

Is the MHC a general self-recognition system playing a major unifying role in an organism?

From the review of several recent observations of cell-cell interactions, which occur preferentially in autologous or syngeneic situations such as rosettes, adhesion, homing, and contact inhibition, the existence of an active general process of cellular self-recognition, not limited to the immune system, is postulated. This process is MHC associated or dependent, and seems to require an identity of ubiquitous molecules of class I--or other linked gene products at the surface of interacting cells. In contrast, class II molecules are not apparently implicated in general self-recognition. The immune system is regarded as a late evolution from a self-recognition system. It retains the ability of self-evolution, but possesses the exclusive property of active discrimination against foreignness. The astonishing fact that identity of MHC products seems to be needed for recognition is discussed in the context of various possible mechanisms. From immunological and genetical consideration, it is proposed that the genuine biological role of the MHC would be that of a self-recognition and unifying system.     

Preoperative prognostic nutritional index is a significant predictor of survival in patients with localized upper tract urothelial carcinoma after radical nephroureterectomy

Background

Patient's nutritional and immunological status have a potentially significant role in survival outcome in patients with malignant tumors. We investigated the prognostic value of preoperative prognostic nutritional index (PNI) in patients with localized upper tract urothelial carcinoma (UTUC) undergoing radical nephrouretectomy (RNU).

支气管肺泡灌洗液T淋巴细胞亚群及肿瘤标志物检测在肺癌诊断中的应用价值

目的探讨支气管肺泡灌洗液T淋巴细胞亚群及肿瘤标志物检测在肺癌诊断中的应用价值。方法选取50例在我院就诊的肺癌患者为观察组,并选取同期在我院就诊的肺部良性病变患者30例为对照组。两组患者均予以行支气管肺泡灌洗,收集支气管肺泡灌洗液检测血清T淋巴细胞亚群、肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)及鳞状细胞癌相关抗原(SCC)。观察并比较两组肺泡灌洗液T淋巴细胞亚群及肿瘤标志物水平的差异。结果观察组患者支气管肺泡灌洗液T淋巴细胞CD3~+、CD4~+水平明显低于对照组,CD8~+水平明显高于对照组,CD4~+/CD8~+水平明显低于对照组,差异有统计学意义(P0.05或P0.01);观察组患者支气管肺泡灌洗液肿瘤标志物CEA、CYFRA21-1、SCC水平均明显高于对照组,差异有统计学意义(P0.01)。结论肺癌患者免疫功能低下,辅助性T淋巴细胞减少,细胞毒性T淋巴细胞增加,检测支气管肺泡灌洗液T淋巴细胞亚群及肿瘤标志物能为临床诊断肺癌提供依据。