[Migration of CD4+ and CD8+ lymphocytes into the internal lining of tuberculous pleural empyema and tuberculous caverns during their local sanitation]. / Migratsiia CD4+- i CD8+-limfotsitov vo vnutrenniuiu vystilku tuberkuleznoi émpiemy plevry i tuberkuleznoi kaverny pri ikh lokal'noi sanatsii.

Cytological, immunological, and microbiological findings after sanitation of pulmonary caverns and pleural empyemas were analyzed in 13 patients: 7 with empyemas of residual pleural cavities after surgery for pulmonary tuberculosis and 6 with fibrocavernous pulmonary tuberculosis. It has been found that target sanitation of the intrapulmonary and intrapleural cavities enhances lymphocytic penetration into the internal part of the cavitary wall, infiltrating lymphocytes represent mainly CD4+ cells whose count progressively increases with successful sanitation, as appeared as a significant rise in both the so-called immunoregulatory index (CD4+/CD8+ ratios of 3.4 to 6.1). A study of the populational composition of lymphocytes promotes an objective evaluation of the magnitude of a specific tuberculous inflammatory process in the wall of the cavity of empyemas and caverns.

Interleukin-7 and interleukin-12 have different effects in rescue of depressed cellular immunity: comparison of malignant and tuberculous pleural effusions.

The present study attempts to determine the role of interleukin-7 (IL-7) and IL-12 in recovering the functions of the lymphocytes of malignant effusion, in terms of cytokine production, proliferation, and cytolytic activity, compared with lymphocytes from tuberculous pleural effusion. Effusion-associated lymphocytes (EAL) were isolated from tuberculous (tEAL) and malignant (mEAL) pleural effusions. The EAL proliferate response was measured after 3 days in culture. Interferon-gamma (IFN-gamma) production and cytotoxicity against K-562 cells or autologous tumor cells were assessed after 6 days in culture. It was found that the mEAL had depressed proliferation, IFN-gamma production, and cytolytic activity, as compared with tEAL. Stimulation with IL-12 plus IL-2, but not with IL-7 plus IL-2, fully restored the IFN-gamma production of mEAL to that of tEAL levels. In contrast, the proliferate response of mEAL was enhanced significantly more with IL-7 plus IL-2 than with IL-12 plus IL-2. Both the IL-7 plus IL-2 and IL-12 plus IL-2 stimulation of mEAL showed a significant increase in cytolytic activity against autologous tumor cells, although the cytolytic activity against K-562 cells did not increase. These results suggest that tEAL had a higher cellular activity than mEAL. This depressed cellular function of mEAL could be reversed with cytokines. However, different cytokines had different effects on mEAL; for example, IL-7 had a better effect in the stimulation of lymphocyte proliferation compared with IL-12, which had a better effect in driving the lymphocytes to the T helper 1 (TH1) pathway and a higher IFN-gamma production. Both IL-7 and IL-12, in the presence of IL-2, can restore the immunosuppressed cytolytic activity of the lymphocytes of malignant pleural effusion against autologous tumor.

Elevated interleukin-2 receptor level in patients with active pulmonary tuberculosis and the changes following anti-tuberculosis chemotherapy.

Soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation. We have undertaken a study to examine the serum sIL-2R levels in patients with pulmonary tuberculosis (TB) and the changes following anti-TB chemotherapy. Forty four patients with pulmonary TB or tuberculous pleural effusion were recruited. Serum was collected from the patients before and at 1, 2, 4 and 6 months after initiation of anti-TB chemotherapy. Serum sIL-2R level was measured by an enzyme immunoassay. The mean sIL-2R level before treatment was 1,452 +/- 103 (SEM) U.ml-1, which was significantly higher than that of healthy control subjects (374 +/- 30 U.ml-1). There was no significant change in the sIL-2R level at 1 month, but there was a gradual reduction from the second month onwards. At the sixth month the mean sIL-2R level was 1080 +/- 81 U.ml-1, which was significantly lower than that before treatment. However, despite clinical improvement, the sIL-2R levels at the sixth month were still significantly higher than those of control subjects. We conclude that sIL-2R levels were elevated in patients with pulmonary TB and there was a gradual reduction following anti-TB chemotherapy. However, the sIL-2R levels were still higher than control subjects at completion of treatment, suggesting a delayed resolution of the inflammation in patients with pulmonary TB.

High expression of the Epstein-Barr virus latent protein EB nuclear antigen-2 on pyothorax-associated lymphomas.

Pyothorax-associated lymphoma (PAL) is a rare tumor associated with long-standing tuberculous pyothorax. Most of these lymphomas are B-cell lymphomas of high-grade malignancy. Over 50 cases have been reported in Japan, but no cases have been described in Western countries. Its pathogenesis remains unknown. We studied immunohistologically the expression of Epstein-Barr virus- (EBV) encoded latent gene products, EB nuclear antigen-2 and LMP-1, in four cases of PAL. Fifty B-cell lymphomas unrelated to pyothorax, and five EBV-bearing lymphoblastic tumors produced in severe combined immune deficient mice (severe combined immune deficient-EBV+ tumors) were also studied as controls. Marked expression of EB nuclear antigen-2 was demonstrated on all four PALs. LMP-1 was also present in all cases, but both the staining intensity and the number of stained cells remained less than on severe combined immune deficient-EBV+ tumors. Neither EB nuclear antigen-2 nor LMP-1 was observed in the 50 control B-cell lymphomas. Additional molecular genetic analysis revealed that EBVs are incorporated into each PAL clonally. These results confirm the definite association of EBV with PALs, although the significance of weak expression of LMP-1 awaits further study.

PPD-specific proliferative response in humans. I. Analysis of PPD-specific proliferative cells from tuberculous pleurisy patients and healthy controls with monoclonal antibodies specific for human T subsets.

Peripheral mononuclear cells (PBL) from tuberculin reaction (TR)-negative tuberculous pleurisy patients proliferated poorly with PPD, while the cells of pleural effusion from these patients showed a proliferative response to PPD as well as did the healthy control PBL. Surface antigens of peripheral blood and pleural effusion were examined by using monoclonal antibodies. The Leu 1-positive cell population can be divided into four groups, namely (1) Leu 1+, Leu2a+, Leu 3a+, (2) Leu 1+, Leu 2a+, Leu 3a-, (3) Leu 1+, Leu 2a-, Leu3a+, and (4) Leu 1+, Leu 2a-, Leu 3a- cell populations. Results of analysis of surface antigens of PPD-specific proliferative cells in peripheral blood and pleural effusion from tuberculous pleurisy patients as well as healthy controls indicate that the PPD-specific proliferative response is mediated by Leu 1+, Leu 2a-, Leu 3a+ cells and Leu 1+, Leu 2a-, Leu3a- cells.

In vitro restoration by thymosin of T lymphocytes from patients with lung tuberculosis.

The percentage of E-rosette forming T-lymphocytes is considerably decreased in a number of patients with severe form of lung tuberculosis, particularly in those with tuberculous empyema of the pleura (28.5% to 38%). After in vitro incubation of lymphocytes from those patients with thymosin V fraction T-lymphocytes restored normal.

[Immunomorphological aspects of nonspecific bronchitis in pulmonary tuberculosis]. / Immunomorfologicheskie aspekty nespetsificheskogo bronkhita pri tuberkuleze legkikh.

Bronchi of the lungs resected for tuberculosis were examined histotopographically, morphometrically and immunohistologically. The greatest number of cells in the mucous membrane of the bronchi and the greatest extent of hypertrophy of bronchial glands were found in the stage of progression of lung tuberculosis, while normalization of the quantitative values-in the stage of remission. In the stage of progression the cellular infiltrate was characterized by marked pyroninophilia, abundance of blast cells and antigen specificity; when the process stabilises, plasmocytes are predominant in the infiltrate. In chronic tuberculosis, lymphonodules are frequently found in the bronchial wall. The above morphological signs of hypertrophic bronchitis are regarded as manifestations of immunity reactions (cellular, humoral, secretory) induced by penetration into the bronchi of the antigen-containing detritis from destructive foci.