Characterization of local memory cells in stage-classified pulmonary tuberculosis: preliminary observations.

Immunophenotype analysis and proliferative responses were investigated in bronchoalveolar lavage (BAL) cells from 21 patients with stage-classified tuberculosis: six with localized pulmonary infiltrate (LPI); seven with diffuse pulmonary infiltrate (DPI); and eight with pleural effusions (PE). Bronchoalveolar lavage cells from these patients contained a high number of cells/ml. The macrophage number was significantly lower in the DPI group (P < 0.05) compared to the LPI or PE groups. Conversely, neutrophils were markedly increased in DPI patients compared to LPI (P < 0.01) and PE (P < 0.01) patients. Lymphocyte infiltration (97.7 +/- 2.3% CD3+, > 83% alphabeta+ and CD4+ > CD8+) was observed in the three groups. A significant increase in the number of total lymphocytes (P < 0.01) and CD4+ cells (P < 0.05) was observed in the LPI group compared to the PE group. In the LPI group CD4+CD45RO+ cell infiltration was higher than CD4+CD45RA+ cells (P < 0.001), contrasting to similar numbers of these subpopulations in the DPI group. Lymphocytes from three out of three LPI patients (alphabeta+CD4+CD45RO+) responded against tuberculin purified protein derivative contrasting to the unresponsiveness of five patients with either DPI or PE. This impaired response was reverted in two out of five patients by using peripheral blood monocytes instead of alveolar macrophages. It is suggested that, in humans, alphabetaCD4+CD45RO cells are the main lymphocyte type involved in the initial local cell-mediated immune response against Mycobacterium tuberculosis.

Failure of cell-mediated effector mechanisms in lung cancer.

The status of cell-mediated effector mechanisms was studied in 28 patients with lung cancer (25/28 in stage III). Patients' precultured peripheral blood mononuclear leukocytes, isolated by Ficoll-Hypaque, were tested for lymphocyte proliferation responses to alloantigens in mixed lymphocyte culture (MLC). The influence of autologous patients' sera was studied further on MLC responses from patients and controls. Cell-mediated lympholysis (CML), with the use of allogenic blast cells as targets, and antibody-dependent cell-mediated cytotoxicity (ADCC) against human red blood cells also were tested. Major differences between the cancer patients and controls were not demonstrated by MLC. Inhibition or enhancement of MLC responses by the autologous serum was shown; bimodal influence was significant; 72% of the sera caused inhibition and 28% caused enhancement. CML was depressed in 54% of the patients, and ADCC was depressed in 50%. The decrease in both cytotoxic responses was significant (P less than .005). Thirteen patients died after initiation of the investigative protocol; in 11 of 13, CML or ADCC was diminished. The altered cytotoxic capabilities were more prevalent among the epidermoid type, including the deceased patients. This study provides evidence that a severe impairment of cell-mediated effector mechanisms is frequent in advanced lung cancer and may be associated with poor clinical course and with the histologic type.