Structural and functional consequences of alveolar cell recognition by CD8(+) T lymphocytes in experimental lung disease

CD8(+) T cells infiltrate the lung in many clinical conditions, particularly in interstitial lung disease. The role(s) that CD8(+) T cells might be playing in the pathogenesis of inflammatory lung disease is unclear at present, as is the direct contribution of CD8(+) T cell effector activities to lung injury. This report describes a transgenic model used to evaluate the impact, on respiratory structure and function, of CD8(+) T lymphocyte recognition of a target antigen expressed endogenously in alveolar epithelial cells. We found that adoptive transfer of cloned CD8(+) cytotoxic T lymphocytes (CTLs) specific for an alveolar neo-antigen (influenza hemagglutinin) leads to progressive lethal injury in transgenic mice, which dramatically affects lung structure and function. Transgenic recipients of CD8(+) CTLs exhibited tachypnea and progressive weight loss, becoming moribund over a period of several days. Concomitantly, the animals developed a progressive interstitial pneumonitis characterized initially by lymphocytic infiltration of alveolar walls and spaces, followed by an exuberant mononuclear cell infiltration that correlated with restrictive pulmonary mechanics and a progressive diffusion impairment. These results indicate that antigen-specific CD8(+) T cell recognition of an alveolar epithelial "autoantigen" is, in and of itself, sufficient to trigger an inflammatory cascade that results in the histological and physiological manifestations of interstitial pneumonia.     

Reduction of islet amylin expression and basal secretion by adenovirus-mediated delivery of amylin antisense cDNA

A 55-year-old woman was admitted to our hospital with progressive dyspnea that had begun one month before. Chest rentogenogram revealed groundglass appearance and reticular shadows bilaterally. Pulmonary function tests showed both decreased vital capacity and diffusing capacity. Bronchoalveolar lavage fluid had a high lymphocyte fraction with a low CD4+/CD8+ ratio. Thoracoscopic lung biopsy revealed thick, fibro-edematous interstitium and diffuse infiltration of lymphocytes. We also observed an intra-alveolar exudate with infiltration of histiocytes and lymphocytes. The clinical features and pathological findings were consistent with subacute interstitial pneumonia, which was the entity proposed by Kawabata and colleagues. The patient developed acute respiratory failure four days after lung biopsy and died despite steroid pulse therapy. Although subacute interstitial pneumonia has been reported to respond to steroid therapy, and to have a good prognosis, we believe that subacute interstitial pneumonia could fatally worsen when associated with lung biopsy, infection, or some other stimulus.     

An Analytical Formula for the Energy of the Bound Long-Range 0(-)g((1)3Pig) State of Cs2

In an asymptomatic 4 yr old child with radiographic evidence of parenchymal lung disease, bronchoalveolar lavage (BAL) yielded the diagnosis of chronic lipid pneumonia caused by chronic aspiration of mineral oil given as a laxative. BAL analysis showed a marked reduction in the total number of alveolar macrophages; almost 70% of these cells contained intracytoplasmic lipid vacuoles. It also disclosed lymphocytic (cytotoxic/suppressor) alveolitis. A high percentage of lymphocytes expressed antigen markers of activation (human leucocyte antigen (HLA)-DR), CD54 and CD25). BAL analysis 18 months after mineral oil intake revealed that lymphocytes bearing antigen markers of activation had markedly decreased whereas alveolar macrophages (normal and lipid-laden) had increased. A subsequent whole lung BAL was considered unnecessarily invasive in this otherwise healthy child.     

Interstitial pneumonitis in bone marrow transplant recipients is associated with local production of TH2-type cytokines and lack of T cell-mediated cytotoxicity

BACKGROUND: Interstitial pneumonitis, especially associated with cytomegalovirus (CMV) infection, is a serious complication after bone marrow transplantation (BMT), with a high fatality rate despite adequate antiviral treatment. The aim of this study was to elucidate the local immunopathogenesis of interstitial pneumonitis caused by CMV or other agents in BMT recipients. METHODS: Cryopreserved lung tissue obtained from 12 patients with interstitial pneumonitis following BMT was analyzed for cytokine production at the single-cell level using a cytokine-specific monoclonal antibody and immunohistochemical technique. Cytokine production in individual cells was analyzed using monoclonal antibodies to 23 different human cytokines: interleukin (IL)-1 to IL-13, tumor necrosis factor (TNF)-alpha, TNF-beta, interferon-gamma (IFNgamma), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)-beta1 to 3. RESULTS: Marrow transplant patients with interstitial pneumonia had increased numbers of infiltrating alveolar macrophages, CD3+, CD4+ T cells, and CD40+ B cells and significantly increased numbers of IL-4-, IL-10-, IL-1-, TGF-beta1-, TGF-beta2-, and TGF-beta3-producing cells than controls. IL-2-, IFN-gamma-, and TNF-beta-producing cells were undetectable in most patients with CMV pneumonitis (n=7). Neither perforin-positive CD8+ T lymphocytes nor up-regulation of the apoptotic pathway was detected in lung tissue from patients with interstitial pneumonia. In contrast, extensive local production of IgA, IgG, and IgM was demonstrated in all patients. Intracellular and extensive extracellular deposition of CD68, the L-1 antigen synthesized in CD14+ macrophages, was found. CONCLUSIONS: The cytokine profile suggested that Th1-type cytokine production was absent, whereas production of Th2-type cytokines was significantly up-regulated. Interstitial pneumonitis in BMT recipients with fatal outcome (11/12 patients) was associated with dysregulation in the local cytokine network notable for a predominant Th2 immune response with minimal or absent T cell-mediated cytotoxicity.     

Bronchiolitis obliterans with organizing pneumonia in a patient treated with amiodarone]

Bronchiolitis obliterans organizing pneumonia (BOOP) is a well-defined clinicopathological entity. The aetiology of BOOP is generally unknown, although it has been associated with specific diseases or various pharmaceutical drugs. The amiodarone is one of them. We report a patient with BOOP secondary to amiodarone therapy, who presented with cough, fever and sputum production, dyspnoea and night sweats lasting for two months. A chest radiograph showed bilateral patchy and interstitial infiltrates. Lymphocyte phenotyping of bronchoalveolar lavage fluid showed decreased ratio of CD4+:CD8+ lymphocytes. Transbronchial lung biopsy established the diagnosis of BOOP. After stopping amiodarone therapy, symptoms disappeared and the chest radiograph remained normal within two months.     

Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice

The role of IFNgamma in the development of infection-driven interstitial pneumonitis in a model of murine graft-versus-host disease was investigated. Mice were given either syngeneic or allogeneic bone marrow transplants along with lung Pneumocystis carinii infections and were treated with either control mAb or anti-IFNgamma mAb. At day 21 after transplant, lung weights were elevated nearly twofold in all groups. By day 41, mice in all groups had cleared the P. carinii but only the mice given allogeneic transplants and anti-IFNgamma had increased lung weights. Increased lung weights in the anti-IFNgamma-treated mice corresponded to alveolar infiltration of eosinophils, neutrophils, and multinucleated giant cells and exacerbated interstitial pneumonitis compared with mice treated with control antibody. Intracellular staining indicated that there were 3- to 10-fold more CD4+ cells producing IFNgamma than those producing IL-4 in the lung lavages of mice given either syngeneic or allogeneic transplant. Treatment of transplanted mice with anti-IFNgamma resulted in a significant decrease in IFN-gamma-producing CD4+ and CD8+ cells in the lung lavages but no change in the number of IL-4-producing CD4+ cells. These data indicate that IFNgamma is critical for controlling the development of P. carinii-driven interstitial pneumonia after either syngeneic or allogeneic bone marrow transplant in mice.     

A comparison of the antigen-presenting capabilities of class II MHC-expressing human lung epithelial and endothelial cells

Human lung alveolar epithelial cells constitutively express class II major histocompatibility complex (MHC). Human lung microvascular endothelial and small airway epithelial cells can be induced to express class II MHC by stimulation with the pro-inflammatory cytokine interferon-gamma. The levels of class II MHC on lung epithelial and endothelial cells were comparable to those seen on an Epstein-Barr virus (EBV)-transformed B-cell line. However, the costimulatory molecules B7-1 and B7-2 were not expressed. The ability of the class II MHC expressing human lung parenchymal cells to present alloantigen to CD4+ T lymphocytes was investigated. Freshly isolated human alveolar epithelial cells (type II pneumocytes) and monolayers of interferon-gamma-stimulated small airway epithelial and lung microvascular endothelial cells were co-cultured with allogeneic CD4+ T lymphocytes and proliferation determined by [3H]thymidine incorporation. A clear difference was observed between effects of the epithelial and endothelial cells on CD4+ T-lymphocyte activation. Alveolar and small airway epithelial cells failed to stimulate the proliferation of allogeneic CD4+ T lymphocytes whereas lung microvascular endothelial cells did stimulate proliferation. This difference could not be explained by the levels of class II MHC or the lack of B7-1 and B7-2 solely. Microvascular endothelial cells, and not alveolar or small airway epithelial cells, possess B7-independent costimulatory pathways.     

Establishment of an animal model for pulmonary fibrosis in mice using monocrotaline

A preliminary attempt at experimental induction of pulmonary fibrosis in which male ICR mice received 15 weekly sc injections of 200 or 100 mg/kg monocrotaline (MC) revealed that most animals treated with the larger dose died of severe interstitial pneumonia, whereas those given 100 mg/kg exhibited only relatively slight lung injury. Based on these results, male mice were administered sc injections of 200 and 100 mg/kg MC once a week for 9 and 18 times, respectively, and then maintained without any further treatment until week 28 after the start. Mice treated with 200 mg/kg MC showed severe pulmonary damage and died by week 25. Mortalities also occurred in the 100-mg group from week 16, with 11 of 40 animals surviving at the termination of the experiment. Histologically, both dose groups demonstrated severe interstitial pneumonia and/or pulmonary fibrosis. Ultrastructurally, inflammatory edema possibly attributable to injuries of alveolar capillary endothelial cells was observed in the high-dose group at week 8, and there was a remarkable increase in collagen fibers in alveolar septa in this group thereafter. The present study results suggest that lung injuries induced by MC treatment progress to irreversible lung fibrosis and that this animal model may have advantage for studying the pathogenesis of lung cancers in patients with pulmonary fibrosis.     

Adverse effects of a single dose of (+)-sotalol in patients with mild stable asthma

The case history of a 25-year-old man suffering from idiopathic alveolar proteinosis is described. The patient showed a prolonged stable mild disease and a distinct suppressive phenotypic profile of BALF lymphocytes. Specifically, a low T4/T8 ratio and a high percentage of CD11b+ T8 lymphocytes was found. Correlations with disease expression are made.     

A case report of pneumonia due to Chlamydia trachomatis with pleural effusion

A 64-year-old male consulted our hospital with a 6-day history of malaise, body temperature to 38 degrees C, anorexia, and light headedness. The chest radiograph showed consolidation in the left lower lung area. Chest CT and ultrasonography revealed left pleural fluid. The pleural fluid was exudative (yellowish in color, protein 3.0 g/dl, Rivalta reaction positive, adenosine deaminase 19.4 U/L), and had a total cell count of 4.7 x 10(6)/ml with 45% lymphocytes, 40% histiocytes, and 15% polymorphonuclear leukocytes. He had kept a budgerigar, but we could not isolate Chlamydia from the pleural fluid or the pet bird. Transbronchial lung biopsy from left S10 revealed an increase of mononuclear leukocytes within the interstitial spaces, and the alveolar spaces contained polymorphonuclear leukocytes, fibrin, and organized alveolar exudate. Bronchoalveolar lavage cellular constituents were 50% lymphocytes, 27% neutrophils, and 23% macrophages. Serologic studies demonstrated C. trachomatis specific IgM antibody titers at 1:20 in a serum sample and at 1:10 in pleural fluid. We report a case of community-acquired pneumonia caused by C. trachomatis diagnosed by serologic studies.     

IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6)

CBA/J (highly resistant), BALB/c (moderately resistant), and C57BL/6 (susceptible) mice displayed three resistance patterns following intratracheal inoculation of Cryptococcus neoformans 52. The inability to clear the infection correlated with the duration of the eosinophil infiltrate in the lungs. The role of IL-5 in promoting the pulmonary eosinophilia and subsequent inflammatory damage in susceptible C57BL/6 mice was investigated. C57BL/6 mice developed a chronic alveolar, peribronchiolar, and perivascular eosinophilia following C. neoformans infection. This resulted in the accumulation of intracellular Charcot-Leyden-like crystals in alveolar macrophages by wk 4 and the extracellular deposition of these crystals in the bronchioles with associated destruction of airway epithelium by wk 6. IL-5 mRNA was expressed in the lungs, and injections of anti-IL-5 mAb prevented eosinophil recruitment and crystal deposition but did not alter cryptococcal clearance. Depletion of CD4+ T cells (but not CD8+) ablated IL-5 production by lung leukocytes in vitro and eosinophil recruitment in vivo. Neutralization of IL-5 also inhibited the recruitment of macrophages, CD8+ T lymphocytes, and B lymphocytes by 47 to 57%. Anti-IL-5 mAb inhibited CD4+ T lymphocyte recruitment by 30% but did not affect neutrophil recruitment. Thus, the development of a chronic eosinophil infiltrate in the lungs of C. neoformans-infected C57BL/6 mice is a nonprotective immune response that causes significant lung pathology. Furthermore, IL-5 promotes the recruitment and activation of eosinophils, resulting in the recruitment of additional macrophages and lymphocytes into the lungs.     

Differential induction of inositol phosphate metabolism by three adipokinetic hormones

Sheep naturally infected by visna-maedi virus often develop a chronic interstitial lung disease characterized by an alveolitis comprising lymphocytes, neutrophils and macrophages. The alpha chemokine interleukin-8 (IL-8) was detected in cell free bronchoalveolar lavage fluid from naturally infected animals, confirmed by RT-PCR, presenting typical lesions of maedi and elevated total alveolar cell counts. No detectable IL-8 was found in the fluid obtained from uninfected animals. IL-8 concentration in alveolar fluid is correlated with alveolar neutrophil counts. Bronchoalveolar lavage cells from infected animals were found to contain a large amount of IL-8 mRNA and may contribute to IL-8 production. In situ hybridization showed that macrophages were the predominant cell type expressing IL-8 mRNA. Sustained production of IL-8 by alveolar macrophages during visna-maedi infection could suffice for neutrophil attraction to the alveoli, and may contribute to the development of lesions.     

A case of lymphocytic interstitial pneumonia

A 56-year-old female was admitted on November 1995 to our hospital because of the abnormal shadow on her chest X-ray. Although the chest X ray film revealed diffuse reticulonodular shadows in the bilateral lung fields and right hilar lymphadenopathy, she had not any complaints. Furthermore, mediastinal lymphadenopathy and polyclonal hypergammaglobulinemia were noted. For a further examination, transcutaneous thoracoscopic lung biopsy was performed on August 1996. The lung specimens showed a interstitial infiltration of small lymphocytes exclusively around bronchioles. And the diagnosis of lymphocytic interstitial pneumonia (LIP) was made. She had been suffered from bronchial asthma for 27 years. This is the first report of LIP accompanied with bronchial asthma. Its relationship between LIP and bronchial asthma remains unclear. In the 2 years of follow-up, she remained asymptomatic with unchanged chest radiogram. And her pulmonary function was preserved for the 2 years. But lymphocytic interstitial pneumonia may induce malignant lymphoproliferative disease potentially, we should carefully follow up.     

Respiratory symptoms, lung function tests, airway responsiveness, and bronchoalveolar lymphocyte subsets in B-chronic lymphocytic leukemia

A respiratory questionnaire was completed and spirometry, tests for lung volumes, diffusion capacity for CO, and methacholine bronchial challenge were performed in 24 outpatients with B-chronic lymphocytic leukemia (B-CLL), aged 44-79, presenting in different stages of their disease. In 10 patients, bronchoalveolar lavage (BAL) fluid was also obtained. Ten of twenty-four patients had symptoms consistent with chronic bronchitis, unrelated both to smoking history and to the clinical stage. Abnormal values (< 2 SD) were found in 4 patients for total lung capacity (TLC), in 9 for vital capacity (VC), 8 for forced expiratory volume in 1 sec (FEV1), 11 for MEF50, 15 for MEF25 and in 7 for diffusing capacity for carbon monoxide. Seven of nineteen patients had PD20FEV1 at less than 1,600 micrograms of methacholine chloride. There was a significantly negative correlation between white blood cell count and VC (r = 0.41, P < 0.05). A positive correlation was found between PD20FEV1 and FEV1/VC (r = 0.61, P < 0.01). The mean and SEM for BAL cells/ml was 463 (71.8) x 10(3). No leukemic cells but a marked increase in T lymphocytes (32.5 +/- 7.8%) were found in BAL fluid. There were significantly negative correlations between the number of BAL CD3+ T lymphocytes and PD20FEV1 (r = 0.61, P < 0.05), and between the number of BAL CD8+ T lymphocytes and PD20FEV1 (r = 0.84, P < 0.01). In conclusion, patients with B-CLL have a high prevalence of respiratory symptoms, small airway dysfunction and CD8 "alveolitis" related to airway responsiveness; despite the well-known lung interstitial lymphocyte infiltration in B-CLL, leukemic cells are not found in BAL fluid.     

Expression of the CD8alpha beta-heterodimer on CD8(+) T lymphocytes in peripheral blood lymphocytes of human immunodeficiency virus- and human immunodeficiency virus+ individuals

CD8(+) T lymphocytes play a pivotal role in controlling human immunodeficiency virus (HIV)-1 replication in vivo. We have performed four-color flow cytometric analysis of CD8(+) peripheral blood lymphocytes (PBL) from 21 HIV-1 seronegative and 103 seropositive individuals to explore the phenotypic heterogeneity of CD8beta-chain expression on CD8(+) T lymphocytes and to clarify how its expression on CD8(+) T lymphocytes may relate to acquired immunodeficiency syndrome (AIDS) clinical progression. We showed that the single monoclonal antibody (MoAb) 2ST8-5H7, directed against the CD8alpha beta-heterodimer, identifies CD8(+) T lymphocytes as effectively as the conventional combination of anti-CD3 and anti-CD8alpha antibodies. However, we detected a significantly lower mean fluorescence (MF) of anti-CD8alpha beta staining on PBL from HIV-1 seropositive donors as compared with seronegative donors. In fact, CD8(+) T lymphocytes from HIV-1-infected individuals with the lowest CD4 counts showed the lowest levels of CD8alpha beta MF. To explore further this change in CD8alpha beta expression, we assessed the expression of 14 different cell surface molecules on CD8alpha beta+ T lymphocytes of PBL from 11 HIV-1 seronegative and 22 HIV-1 seropositive individuals. The MF of anti-CD8alpha beta staining was significantly reduced on CD8(+) T lymphocyte subsets that showed immunophenotypic evidence of activation. The subset of lymphocytes expressing low levels of CD8alpha beta expressed higher levels of activation, adhesion, and cytotoxic-associated molecules and was predominantly CD45RO+ and CD28(-). Finally, we monitored the expression of the CD8alpha beta-heterodimer on PBL of eight HIV-1-infected individuals over a 16-week period after the initiation of highly active antiretroviral therapy (HAART), including zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV), and found a significant increase in the expression of the CD8alpha beta-heterodimer. These results suggest that antibodies recognizing the CD8alpha beta-heterodimer are useful tools to specifically identify CD8(+) T lymphocytes. Moreover, the quantitative monitoring of CD8alpha beta expression allows the detection of discrete CD8(+) T lymphocyte subsets and may be useful for assessing the immune status of individuals infected with HIV-1.     

Expression of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of the lung with observations on the expression of these adhesion molecules in non-neoplastic lung tissue

Intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and the lymphocyte function-associated antigen (LFA-1) are cell adhesion molecules thought to play an important role in the complex process of airway inflammation and tumor cell growth. The aim of this study was to examine the distribution of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of lung and in major cellular compartments of non-neoplastic lung tissue. We examined cellular compartments in tissue from five bronchoalveolar carcinomas, three acinar adenocarcinomas, and one colon cancer metastatic to the lung. The compartments in neoplasms included the tumor cells proper, endothelial cells within the tumor vasculature, tumor stromal cells, and tumor-infiltrating lymphocytes. The compartments in non-neoplastic lung tissue included lung endothelial cells, pulmonary lymphocytes, interstitial fibroblasts, Type II alveolar pneumocytes, and bronchial epithelial cells. ICAM-1 was expressed in tumor cells from all of the nine adenocarcinomas. In contrast, VCAM-1 expression was not identified in tumor cells from any of the nine adenocarcinomas. ICAM-1 was expressed in all cellular compartments of the non-neoplastic lung tissue, whereas VCAM-1 was expressed only in pulmonary lymphocytes and interstitial fibroblastic cells. LFA-1 was uniformly expressed in tumor-infiltrating lymphocytes from each of the nine tumors and all of the lymphocytes in non-neoplastic lung tissue. This study showed major differences in the expression of ICAM-1 and VCAM-1 in tumor cells from pulmonary adenocarcinoma and also provided evidence for a wider distribution of ICAM-1, compared with VCAM-1, in non-neoplastic cellular compartments of the lung. ICAM-1 expression was particularly noticeable in bronchial and alveolar epithelial cells. Upregulation of ICAM-1 in pulmonary adenocarcinoma might foster binding by LFA-1-bearing lymphocytes, with a possible impact on the vulnerability of tumor cells to host defense mechanisms.     

Platelet activating factor (PAF) in memory formation: role as a retrograde messenger in long-term potentiation

A model of experimental infection with EV1, a British isolate of maedi-visna virus (MVV), has been developed. Twelve male Texel sheep were allocated to three groups and inoculated by the respiratory route with different inocula. Six of the animals received 10(7.2) tissue culture infective dose (TCID50) of MVV EV1 strain. Two sheep were inoculated with the same dose of heat inactivated MVV EV1 strain. An additional group of four sheep was sham-inoculated with identically prepared virus-free culture media. Experimental infection was followed for 16 weeks. Prior to inoculation, routine haematology, bronchoalveolar lavage (BAL) and flow cytometric analysis of bronchoalveolar lavage fluid (BALF) lymphocytes were performed in all animals to provide baseline parameters. Flow cytometric analysis of BALF lymphocytes and differential BALF cell counts were performed. Precipitating antibodies to MVV developed in all MVV-inoculated animals during the first 4 weeks post-inoculation, while the rest remained seronegative to MVV. MVV-infected animals had significantly decreased (P < 0.05) percentages of macrophages and significantly increased (P < 0.05) percentages of lymphocytes in BALF 4 weeks post-inoculation. Phenotypic changes in BALF T lymphocytes from MVV-inoculated animals, compared with the other two groups, showed significantly decreased (P < 0.05) percentages of CD4+ and gamma delta + T lymphocytes, significantly increased (P < 0.05) percentages of CD8+ lymphocytes and significant inversion (P < 0.05) of the CD4+/CD8+ ratio at different sampling times, but between 2 and 12 weeks post-inoculation. These findings indicate that during experimental MVV-infection an early, short-term cellular reaction occurs in the lung, that is characterised by T lymphocyte phenotypic changes that are very similar, if not identical, to those observed in natural MVV infection.     

Tumour radiosensitization by high-oxygen-content gases: influence of the carbon dioxide content of the inspired gas on PO2, microcirculatory function and radiosensitivity

The rat testis is considered to be an immunologically privileged site because of its reduced capacity to support antigen-specific immune responses. To understand this phenomenon, it is essential to characterize both the lymphocyte subpopulations normally present in the testis and their regulation by testicular cytokines. Peripheral blood was obtained from adult male Dark Agouti or Sprague-Dawley rats, and testicular interstitial tissue was collected after perfusion of the testes to remove blood. Blood and testis lymphocytes were isolated using discontinuous Percoll density gradients, and the testicular lymphocytes were further purified by selective adherence to remove mononuclear phagocytes. The isolated lymphocytes were analyzed by flow cytometry using specific monoclonal antibodies and fluorescein labeling and were enumerated as total T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells. In contrast to peripheral blood, in which the CD4+ T-cell subset was the major lymphocyte subset, rat testis T cells were predominantly of the CD8+ subset, and a large population of NK cells also were present. Subsequently, peripheral blood lymphocytes were stimulated with the polyclonal T-cell activator, phytohemagglutinin, and cultured in the presence of activin, inhibin, or transforming growth factor beta (TGFbeta) prior to flow cytometric analysis. Activin and TGFbeta suppressed T-cell proliferation without any selective effect on either T-cell subset, and inhibin had no effect. The predominance of CD8+ T cells and NK cells, and the relatively minor proportion of CD4+ T cells, are consistent with both increased cellular immune surveillance and a reduced capacity for initiating antigen-specific immune responses in the adult rat testis.     

Effect of haemoglobin concentration on brain oxygenation in focal stroke: a mathematical modelling study

A 56-year-old woman was admitted to the hospital because of dry coughing and shortness of breath on exertion. In addition, dry eyes and cornea guttata suggested Sj?gren's syndrome. Chest radiography revealed linear, reticular shadows throughout the lung fields, and enlargement of hilar and mediastinal lymph nodes. A specimen was obtained by transbronchial lung biopsy but the findings were not condusive; open-lung biopsy was done. The histopathological findings suggested lymphocytic meterstitial pneumonia. Results of genetic analysis and of immuno-histochemical examination conformed that the proliferating lymphocytes were polyclonal. Corticosteroids and immunosuppressive drugs have been used to treat lymphocytic interstitial pneumonia, and they were effective in this case.