The role of Vdelta2+T-cells in patients with active Mycobacterium tuberculosis infection and tuberculin anergy.

SETTING: Tuberculosis (TB) is one of the most common major infectious diseases. In humans, acquired protective immunity to Mycobacterium tuberculosis depends on T-cells and involves multiple T-cell subsets; however, the pathways used by T-cells to restrict the growth of M. tuberculosis are poorly understood. OBJECTIVE: To investigate the possible role of Vdelta2+T-cells and regulatory T-cells in the immune response to M. tuberculosis. As Vdelta2+T-cell function has been shown to be impaired in patients with M. tuberculosis infection, we investigated the percentage of perforin and Fas ligand (FasL) positive Vdelta2+T-cells and the possible role of activating and inhibitory natural killer (NK) cell receptors as well as that of regulatory T-cells in the control of tuberculin responsiveness. RESULTS: Tuberculin-negative patients demonstrated decreased perforin expression and increased FasL expression, which could not be explained by dysregulation of NK cell receptor expression or altered regulatory T-cell function. CONCLUSION: Altered cytotoxic capacity and apoptotic potential of Vdelta2+T-cells provide a plausible explanation for defective cellular immune functions in M. tuberculosis-infected anergic patients.

Gamma/delta T cell subsets in patients with active Mycobacterium tuberculosis infection and tuberculin anergy.

Earlier data suggest that gamma/delta T cells may play an important role in the immune response to Mycobacterium tuberculosis. The aim of this study was to determine the percentage of different gamma/delta subsets in peripheral blood of active tuberculosis patients with a positive or negative tuberculin reaction. Thirty-eight patients infected with M. tuberculosis and 22 healthy controls were included in the study. Venous blood was taken before starting antimycobacterial treatment. Lymphocytes were reacted with monoclonal antibodies specific for different gamma/delta V chains (Vdelta1, Vdelta2, Vgamma9 and Vgamma4). The results were analysed in the context of tuberculin reactivity and X-ray findings. Our results revealed a selective loss of Vgamma9/Vdelta2 T cells in the peripheral blood of tuberculin-negative patients with active tuberculosis compared to healthy controls, while the ratio of Vgamma9/Vdelta2 T cells in the peripheral blood of patients with a positive skin test did not differ from that of healthy controls. These findings demonstrate a relationship between the loss of the major M. tuberculosis-reactive subset of gammadelta T cells and the absence of tuberculin reactivity. The data are consistent with the hypothesis that gammadelta T cells play a role in the protective immune response to M. tuberculosis infection.

Different manifestations of langerhans cell histiocytosis affecting two members of a family.

Two different manifestations of Langerhans cell histiocytosis (histiocytosis X) are presented, the first occurring as a solitary rib eosinophil granuloma in an 11-year-old girl, and the second as an eosinophil granuloma of the lung of her mother, a 41-year-old heavy smoker, appearing 8 years after the onset of her daughter's disease. Familial clustering of two different manifestations of histiocytosis X disease is very rare and raises the possibility of inherited mutations that promote emergence of clonal Langerhans cells.

Th2 biased immune response in cases with active Mycobacterium tuberculosis infection and tuberculin anergy.

This study was aimed at investigating the immunologic relationship between cytokine production pattern and tuberculin negativity in patients with active Mycobacterium tuberculosis infection. After classifying patients by the extent of pulmonary involvement and the size of the tuberculin reaction, we evaluated the rate of cytokine positivity in peripheral blood to determine whether there is a characteristic cellular immune reaction pattern which could partly explain the tuberculin negativity in some of these cases. The significance of tuberculin anergy occurring in some cases with M. tuberculosis infection is still not clear. We investigated the ratio of IL- 4, IL-10, IL-12, CD-4, CD-8 expressing lymphocytes in the peripheral blood of patients with active M. tuberculosis infection and correlated the percentage of the reactive cells with the positivity or negativity of tuberculin skin reactions. Twenty-eight patients were included in the study, with 11 healthy volunteers serving as controls. 10 ml of venous blood was drawn before starting anti-mycobacterial treatment. A tuberculin skin test was performed, introducing intracutaneously 5 TU PPD on the forearm with results evaluated after 72 h. Consistent with the reactivity or non-reactivity of the tuberculin skin test, we found a significantly higher ratio of IL-4 and IL-10 positive lymphocytes and a significantly lower ratio of IL-12 in the peripheral blood of patients with tuberculin anergy than in that of tuberculin positive patients or healthy donors. There was no difference in the ratio of the CD-4 CD-8 positive lymphocytes among the three groups. To evaluate whether the differences could be explained by the degree of pulmonary tubercular involvement, we classified the patients into three groups according to the extent and type of X-ray findings. Seven out of eight tuberculin negative patients were classified as grade III, whereas in the tuberculin positive group only seven out of 20 fell in this category. There was no significant correlation between the radiological grade of the patients and the examined in vitro parameters unless the tuberculin reactivity of each patients was also considered. Tuberculin anergy may reflect an inappropriate immune response to the intracellular pathogen. The high percentage of IL-4 and IL-10 positive lymphocytes together with a low percentage of IL-12 positive lymphocytes in the peripheral blood of anergic patients suggests a Th2 biased immune response during the early course of the disease.

[Chronic obstructive respiratory diseases: diagnosis and therapy]. / Az idült obstruktív légúti betegségek: diagnózis és terápia.

It is estimated there are about one half million people suffering from chronic obstructive pulmonary disease (COPD) today in Hungary. Description of the disease and aspects of the differential procedure used in its diagnosis are here presented. It is crucial to provide individualized treatment for patients with COPD, but smoking is the most important cause of the disease; thus, quitting is the single intervention which can slow the progressive course of the disease. The author presents therapies appropriate for both the stable phase of the disease and its acute exacerbations. Using inhalative anticholinergs is the first step in the treatment schedule, with beta(2)-sympaticomimetics recommended if these are insufficient. The next step up the therapy ladder are the retard theophyllins; long-term glucocorticoids, preferentially by inhalation, may also be needed. Depending on the severity of an acute exacerbation of the disease, various antibiotics are indicated. Rehabilitation programs are detailed, with mention also of patient education; hopefully, such a focus will be of increasing importance to both physicians and patients in the near future.

Calcifying liver metastases in a case of primary lung cancer.

A 50-year-old man presented with primary lung cancer with bone lesions and calcifying liver nodi. Two months after stopping chemotherapy, he died. Autopsy revealed multiple organ metastases. Histologically, the calcified nodi in the liver proved to be affected by tumor metastasis.

Gamma/delta T lymphocytes in Mycobacterium tuberculosis infection.

BACKGROUND: Data on the percentage of gamma/delta T lymphocytes in the peripheral blood of patients infected with Mycobacterium tuberculosis are few and contradictory. The percentage of gamma/delta T lymphocytes in the peripheral blood of tuberculin positive and tuberculin negative patients with Mycobacterium tuberculosis infection and healthy controls was compared. METHODS: Thirty six patients infected with Mycobacterium tuberculosis and 11 healthy controls were studied. Lymphocytes were separated, cytocentrifuged onto glass microscope slides, and reacted with anti-gamma/delta monoclonal antibody. The percentage of gamma/delta positive cells was determined by microscopic counting of 300 lymphocytes. RESULTS: No difference was found in the percentage of gamma/delta T lymphocytes between patients and controls. However, when the patients were divided into two groups according to reactivity or non-reactivity in the Mantoux skin reaction a higher percentage of gamma/delta T lymphocytes was found in the peripheral blood of patients with tuberculin anergy than in tuberculin positive patients or controls. CONCLUSIONS: Higher gamma/delta T cell counts are found in tuberculin negative patients with tuberculosis than in tuberculin positive patients or tuberculin positive controls. The high gamma/delta T cell counts in tuberculin anergic patients may reflect a shift in the immune response in a Th2 direction characterised by increased antibody production and decreased cell mediated responses.

[Angiocentric T-cell lymphoma of the lung]. / A tüdö angiocentrikus t-sejtes lymphomája.

Angiocentric T-cell lymphoma of the lung. The case history of a patient with primary angiocentric T-cell lymphoma of the lung having an unusually long survival period (> 10 years) is presented. Attention is paid to the possibilities of differential diagnosis that should be taken into account in the analysis of certain lymphocytic infiltrates of the lung. In accordance with relevant data of the literature, this case shows that pleiomorphic small cell T-lymphomas may have a protracted course, and the disease free periods repeatedly achieved in this patient by irradiation and chemotherapy are thought to be noticeable. Authors refer to some recent findings which may give new insights in the pathobiology of extranodal T-cell lymphomas, and result in recognition of new disease entities.

Expression of an adhesion molecule and homing in B-cell chronic lymphocytic leukaemia: I. Application of the HEV-binding assay to a clinical series.

High endothelial venule (HEV)-binding of peripheral blood mononuclear cells (PBMCs) from 43 patients with B-cell chronic lymphocytic leukaemia (B-CLL) was investigated with a HEV-binding in vitro assay. Immunophenotyping of HEV-adherent PBMCs proved that most of them belonged to the B-cell proliferation. B-CLL cells stringently expressed CD44 molecules (Hermes-1, -3 and H90). The patients were subgrouped according to Binet's classification, as well as according to the organ manifestations, i.e. patients with B-cell monoclonal lymphocytosis of undetermined significance (B-MLUS) and patients with lymphocytosis (LY), lymph node enlargement (LN) and splenomegaly (SM). The HEV-binding activity of the cells was the highest in Binet stage A patients and in patients with B-MLUS (p < 0.05 in B-MLUS versus B-CLL LY, LN, SM). Based on these findings it is suggested that B-CLL patients show not only a clinical and immunophenotypical heterogeneity, but a diverse function of adhesion molecules.

[Prognostic role of immunoglobulin levels in chronic B cell lymphoid leukemia]. / Az immunglobulin mennyiségének prognosztikai szerepe B sejtes chronikus lymphoid leukaemiában.

The authors analyse the prognostic role of the immunoglobulins detected in the sera of 83 patients with B-cell chronic lymphocytic leukaemia. They have found, that the decreased level of IgG, IgA and IgM itself has no significant prognostic role. In those cases, where the IgA level was the lowest at the recognition of the disease, the expected life-span was significantly shorter. As far as the immunoglobulin level and the clinical stage did not show any significant correspondence, the relative reduction of the IgA level at the recognition of the disease can be considered as a poor prognostic sign.

T-lymphocytes bearing Fc-receptors for IgG in B-cell chronic lymphocytic leukaemia.

Peripheral venous blood lymphocytes of 10 untreated B-CLL patients at stages Rai 0-III and of 10 healthy individuals were studied. In B-CLL the absolute number of T lymphocytes present in peripheral blood was similar to that in healthy controls; however, the ratio of T lymphocyte subpopulations in B-CLL was changed in favour of TG cells, the absolute number of which was found to be increased. In B-CLL DNA synthesis of the TG cells in response to PHA stimulation was more intense than in healthy individuals. These observations are discussed in the light of the conflicting reports on the numerical and functional changes in B-CLL T-cells.