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Biomedical subjects

P B Iles

Publications and source records attributed to P B Iles.

11 recordsLinked to original sources
PubMed1992

Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG.

BACKGROUND: Macrophage activation by cytokines provides only a partial explanation of antimycobacterial immunity in man. Because cytolytic T lymphocytes have been shown to contribute to immunity in animal models of intracellular infection, the generation of mycobacterial antigen specific cytotoxic T cells was examined in the peripheral blood of patients with tuberculosis. METHODS: Subjects comprised 36 patients with active tuberculosis (18 newly diagnosed) and 32 healthy volunteers, of whom 25 had had BCG vaccination and seven were Mantoux negative. The ability of purified protein derivative (PPD) stimulated peripheral blood lymphocytes to lyse autologous, mycobacterial antigen bearing macrophages was examined by using a chromium 51 release assay. RESULTS: PPD stimulated lymphocytes from normal, Mantoux positive, BCG vaccinated subjects produced high levels of PPD specific cytolysis, whereas lymphocytes from unvaccinated, uninfected subjects caused little or no cytolysis. The generation of cytolytic T lymphocytes by patients with tuberculosis was related to their clinical state. Those with cavitating pulmonary disease or lymph node tuberculosis generated PPD specific lymphocytes with cytotoxic ability similar to that of those from Mantoux positive control subjects, whereas lymphocytes from patients with non-cavitating pulmonary infiltrates showed poor antigen specific cytolysis. After seven days of stimulation with PPD in vitro, lymphoblasts contained both CD4+ and CD8+ cells. Mycobacterial antigen specific cytolysis was restricted to the CD4+ cell population and was blocked by monoclonal antibodies directed against major histocompatibility class II (MHC) antigens. CONCLUSION: CD4+ cytolytic T cells can lyse autologous macrophages presenting mycobacterial antigen and were found in patients with cavitating pulmonary tuberculosis or tuberculous lymphadenitis and in normal, Mantoux positive control subjects. The ability to generate these T cell responses seems to be a marker for response to mycobacteria and may contribute to tissue damage in tuberculosis. These responses do not provide protective immunity against Mycobacterium tuberculosis but may help in disease localisation.

BCG Vaccine↗
PubMed1990

Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis.

The cytolytic capacity of mycobacterial antigen-stimulated peripheral blood mononuclear cells, from healthy Mantoux-positive volunteers and from patients with tuberculosis was investigated. Polyclonal T cell lines induced by 7 days of stimulation in vitro with PPD or a sonicate of Mycobacterium tuberculosis lysed both autologous macrophages and Epstein-Barr virus (EBV) transformed B cell lines which had been pulsed with mycobacterial antigens, to a greater extent than unpulsed target cells or target cells pulsed with an irrelevant antigen (streptokinase/streptodornase). The killing of mycobacterial antigen-pulsed macrophages and EBV-transformed B cell line targets was inhibited by monoclonal antibodies to MHC class II antigens but not by antibodies directed against MHC class I antigens. PPD-pulsed EBV-transformed lymphoblastoid cell lines (LCL) competitively inhibited the killing of mycobacterial antigen-pulsed macrophages, whereas natural killer (NK) sensitive K562 cells (with or without antigen pulsing) did not inhibit mycobacterial antigen-dependent cytolysis of macrophages. Patients with tuberculosis showed a spectrum of mycobacterial antigen-induced cytolytic capacity. Those with extensive tissue necrosis (e.g. cavitatory pulmonary tuberculosis or caseous, extrathoracic tuberculosis) had high levels while patients with disseminated (miliary) tuberculosis or disease refractory to treatment showed little evidence of mycobacterial antigen induced cytotoxicity. The ability of mycobacterial antigen-stimulated lymphoblasts to kill specific antigen-pulsed autologous macrophages was not significantly different between healthy donors and patients with tuberculosis. However, the 'mycobacterial antigen-specific' component of this cytolysis was significantly deficient (P less than 0.01) in patients. We conclude that mycobacterial antigen-specific cytotoxic T cell responses may play a significant part in the immune response to mycobacterial infection.

Adult↗
PubMed1981

Circulating immune complexes in patients with lung cancer.

Sera from 41 patients with lung cancer and 41 age and sex-matched hospital inpatients with non-malignant disease were tested for the presence of immune complexes using the 125Iodine Clq binding test. All patients were untreated or had recurrences after surgery. An increased Clq binding activity was found in 34% of patients with lung cancer and 24% of patients with non-malignant disease. There was no significant association between increased serum Clq binding activity and histological tumour type or survival but there was an association with the extent of malignant disease. No patient with limited (state 1) disease had raised Clq binding activity but in 42% of patients with extensive disease it was increased. Increased Clq binding activity did not correlate with either an increased total white cell count of ESR. Measurement of Clq binding activity may be of value in serial monitoring of disease progress and response to treatment.

Aged↗
PubMed1981

Multiple bronchial stenoses: treatment by mechanical dilatation.

Four patients with multiple bronchial stenoses are described. Two patients had pulmonary sarcoidosis, the third probably had berylliosis, and the aetiology in unknown in the fourth. Their symptoms included dyspnoea, wheeze, stridor, and frequent chest infections. The bronchial stenoses were demonstrated by tomography, flow volume studies, and bronchoscopy. Corticosteroids were ineffective but improvement followed bougie dilatation at rigid bronchoscopy.

Adult↗
PubMed1980

Intrapleural BCG in operable lung cancer.

In a controlled randomised clinical trial of 92 patients with surgically resected lung cancer, intrapleural BCG had no clear effect on survival. Adverse effects were insignificant.

Adenocarcinoma↗
PubMed1974

Tuberculous lymphadenitis.

A total of 43 episodes of tuberculosis lymphadenitis were treated in 32 adult patients. In 12 instances the affected lymph node was excised without any chemotherapy; there were 10 relapses. The treatment was local excision of the affected lymph nodes together with antituberculosis chemotherapy with at least two drugs in 30 instances; there were no relapses following such therapy.Presumably patients with tuberculosis lymphadenitis are still sometimes treated with surgery alone because that was at one time the orthodox line of surgical teaching. Such a view is out of date: these patients should always be given antituberculosis therapy in addition to any surgical measures.

Adolescent↗