Takafumi Suda

Th1/Th2 profile in peripheral blood in atopic cough and atopic asthma

Background Eosinophilic tracheobronchitis with cough hypersensitivity, abbreviated as atopic cough, is an important cause of chronic cough. The reason for the absence of airway hyper‐responsiveness is unknown, differing from asthma, a Th2 cytokine‐mediated disorder.

Clinicopathological features of chronic hypersensitivity pneumonitis

Objective: Only limited information exists concerning the clinical and pathological features of chronic hypersensitivity pneumonitis (HP) in Japan and elsewhere. We present data on clinicopathological features of chronic HP obtained through a Japanese nationwide survey.

Muramyl dipeptide-Lys stimulates the function of human dendritic cells.

Muramyl dipeptide (MDP)‐Lys (L18), a synthetic MDP analogue derived from bacterial cell walls, has been reported to be a potent immunoadjuvant that enhances protective immunity against pathogens and tumors by stimulating immune‐competent cells, such as monocytes and macrophages. However, it is not known whether MDP‐Lys modulates the function of dendritic cells (DCs), which are the most potent antigen‐presenting cells and play a crucial role in initiating T cell‐mediated immunity. Therefore, we examined the effects of MDP‐Lys on the expression of surface molecules, cytokine production, and antigen‐presenting function of human DCs generated from peripheral blood cells in the presence of interleukin (IL)‐4 and granulocyte‐macrophage colony‐stimulating factor. We found that MDP‐Lys markedly up‐regulated the expression of CD80, CD83, CD86, and CD40, but not human leukocyte antigen‐DR, and stimulated the production of tumor necrosis factor‐α, IL‐6, IL‐8, IL‐10, and IL‐12 (p40) by human DCs in a dose‐dependent manner. Furthermore, MDP‐Lys‐treated DCs showed enhanced antigen‐presenting function compared with untreated DCs, as assessed by an allogeneic mixed lymphocyte reaction. These results suggested that the immunoadjuvant activity of MDP‐Lys in vivo is mediated, in part, by its stimulation of DC function.

Migratory patterns of thoracic duct lymphocytes into bronchus-associated lymphoid tissue of immunized rats

Abstract. Lymphocytes continuously circulate between the bloodstream and lymphoid organs, and their migration into lymphatic tissues presumably occurs through selective mechanisms. Although bronchus-associated lymphoid tissue (BALT) is known as an inductive tissue of the common mucosal immune system, little is known about how effectively the lymphocytes in the blood vessels migrate into the BALT, thereby enabling the BALT to act as an effector tissue in the immunologic responses of the lungs. To analyze whether or not thoracic duct lymphocytes (TDL) from immunized and nonimmunized rats possess different migratory patterns to the BALT, 5-(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)–labeled TDL were injected into rats with BALT hyperplasia that was produced by intratracheal administration of TNP-KLH, and then the number of labeled cells in the BALT were examined by immunohistochemical methods. We studied the following three groups at 12 h after the injection: group A, intraintestinally immunized donors and intratracheally immunized recipients; group B, nonimmunized donors and intratracheally immunized recipients; group C (control group), nonimmunized donors and nonimmunized recipients. Time course studies 0.5, 4, 12, and 24 h after the injection were done in groups A and C. In a cytokinetic study, larger numbers of CFSE-labeled lymphocytes were found at 12 h and 24 h in group A than in group C. At 12 h after the injection, the absolute number of CFSE-labeled lymphocytes per BALT was significantly higher in group A than in group B (p < 0.05), and was lowest in group C. Histologically, there was a marked proliferation of high endothelial venules (HEV), with findings of adhesion and influx of lymphocytes inside the HEV in group A. These observations indicate that the immunized BALT actively recruits immunized TDL through a specific mechanism of lymphocyte-endothelium recognition in HEV, which partially explains the process of BALT development as an effector tissue for local immunity.

Effects of suplatast tosilate on cytokine profile of bronchoalveolar cells in allergic inflammation of the lung

Objective: Suplatast tosilate is an anti‐allergic agent that inhibits IgE antibody production. It appears to have an inhibitory effect on the production of Th2 cytokines (interleukin (IL)‐4, IL‐5) in vitro. In the present study, we investigated the effects of suplatast on eosinophil infiltration and cytokine mRNA expression in bronchoalveolar lavage (BAL) fluid in a Brown Norway (BN) rat model of bronchial asthma.