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Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8+ T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/β2-microglobulin/peptide complexes using two epitopes. Production of interferon-γ by CD8+ T cells in response to plastic-bound monomeric HLA/peptide complex was observed frequently in sustained virus responders (SVR) ( n = 13) against all the peptides, NS31296–1304 (the percentage of responding patients, 61·5%) and core 129–137 (53·8%), while no interferon-γ production was observed in non-responders (NR) ( n = 13) for any of the peptides. Tetramer-staining showed the presence of CD8+ T cells specific for all the peptides except NS31296–1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296–1304 (3/4) and core 129–137 (1/4) in sustained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-γ production by CD8+ T lymphocytes against HCV NS31296–1304 and core 129–137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8+ T cell response in controlling HCV infection. [ABSTRACT FROM AUTHOR]

We established a mouse model in which fatal pneumonia was induced by pneumococcal superinfection following influenza virus infection in chronic Pseudomonas aeruginosa infected mice. In this mouse model, influenza virus infection caused a significant increase in inflammatory cells, cytokines and severe tissue damage in the lungs of these P. aeruginosa infected mice, before pneumococcal infection. Intra- pulmonary virus titres were significantly increased in mice with chronic P. aeruginosa infection, compared with control mice. Neutrophil function analysis showed significant reduction of myeloperoxidase (MPO) activity and lysozyme secretion by influenza virus infection in these mice. Our results suggest that influenza virus infection may play an important role in inducing pneumococcal pneumonia in chronic P. aeruginosa infected mice. Our results suggested that our mouse model is useful for investigating the pathogenesis of influenza virus infection in patients with chronic lung infection. [ABSTRACT FROM AUTHOR]

SUMMARY We previously reported the establishment of a mouse model system of contact hypersensitivity (CHS) to paraphenylemediamine (PPD). In order to analyse the functional contribution of Th2 cytokines, IL-4 and IL-5, in PPD induced CHS, STAT6 deficient (STAT6–/– ) and wild-type control (WT) mice (C57BL/6) were immunized by the topical application of a PPD solution, and then the subsequent skin reactions were examined. Ear swelling was significantly reduced with a delayed peak response in STAT6–/– mice as compared with that of WT mice. A histological analysis showed the infiltration of both eosinophils and neutrophils in the skin of STAT6–/– mice challenged 24 h previously to significantly decrease in comparison with that in the WT mice. The expression of Th2 cytokines (IL-4, IL-5) by ELISA in the PPD-challenged skin tissue specimens as well as the IgE and IgG1 response after challenge were also profoundly reduced in the STAT6–/– mice. The adoptive transfer of the serum obtained from sensitized WT mice for the putative IgE transfer induced a peak response at 3 h and 24 h after challenge. To further investigate the role of mast cells in the induction of PPD-CHS, mast cell deficient W/Wv mice were sensitized with PPD and then were challenged. Maximal ear swelling was detected from 12 to 24 h and another small peak response was observed at 1 h in+/+mice, whereas only a small peak response at 24 h was detected in W/Wv mice. These data indicate that not only Th2 cytokines and IgE but also mast cells play an essential role in the induction of PPD-CHS. [ABSTRACT FROM AUTHOR]

We investigated the role of inflammatory cytokines in a mouse model of chronic Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DPB), and determined the effects of clarithromycin therapy on the production of these cytokines. The concentrations of IL-1β, IL-2, IL-4, IL-5, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) were measured serially in the lungs of mice with experimentally induced chronic respiratory P. aeruginosa infection until 60 days after inoculation. The concentrations of these cytokines during the course of the disease were significantly higher than baseline (before inoculation, P < 0·01 for all cytokines). Clarithromycin significantly inhibited the production of IL-1β and TNF-α in the lung (P < 0·01). The same treatment also reduced the levels of other cytokines, albeit insignificantly. Treatment with anti-TNF-α antibody significantly reduced the number of pulmonary lymphocytes and concentration of IL-1β in the lung (P < 0·01), but did not change the number of viable bacteria. Our findings resemble those detected in bronchoalveolar lavage fluid of patients with DPB and indicate that inflammatory cytokines play an important role in chronic P. aeruginosa lung infection. Our results also show that macrolides modulated the production of these cytokines, ultimately reducing lymphocyte accumulation in the lung. Our data suggest that anti-TNF-α antibody might be a useful new strategy for the treatment of chronic respiratory P. aeruginosa infection. [ABSTRACT FROM AUTHOR]

Studies the effects of macrophage colony-stimulating factor on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii. Enhancement of the phagocytic fungicidal activity of mononuclear cells; Concentration of tumor necrosis factor-alpha in the lung.

We investigated the increase of platelet-associated IgG and complement component, ³CO caused by the in vitro action of anti-platelet MoAbs, and the effect of mouse and human IgG on these events, Anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib MoAbs caused a slight increase of C3, but not of platelet-associated IgG. In contrast, anti-CD9 and anti-Fey II receptor MoAbs caused an increase of both platelet-associated C3 and IgG. In particular, three MoAbs which activated the complement system caused a marked increase of C3. When platelet-rich plasma was treated with aspirin and prostaglandin, before incubation with antibodies, the increase of platelet-associated IgG was inhibited in all cases. In contrast, the increase of platelet-associated C3 was scarcely influenced. These results suggest that the binding to platelets of platelet-activating antibodies caused the increased expression of IgG molecules on the platelet surface and a possible increase of platelet-associated IgG, However, the increase of platelet-associated C3 appeared to depend on specific characteristics of the antibodies tested, such as a complement-activating effect. In addition, intact mouse or human IgG inhibited the increase of platelet-associated C3 caused by complement-activating antibodies, white F(ab') 2 mouse or human IgG had no such effect. This suggested that the Fc portion of IgG may block the increase of C3 mediated by anti-platelet antibodies. [ABSTRACT FROM AUTHOR]

Para-phenylenediamine (PPD) is known to be a common sensitizer of allergic contact dermatitis and contact urticaria. To clarify the mechanism of contact hypersensitivity (CHS) to PPD, we established a mouse model of PPD-induced CHS. BALB/c mice were immunized for 3 consecutive days by painting topically a 2·5% PPD solution on their shaved abdominal skin. On days 5, 7 or 9 after the initial application, the mice were challenged by applications of a 2·5% PPD solution. Maximal ear swelling was determined at 24 h but another statistically significant and smaller ear swelling was observed 1 h after challenge with PPD in a hapten-specific manner. Adoptive cell transfer experiments demonstrated that the ear swelling of the adoptive cell transferred mice displayed an early response at 6 h and a late response from 12 h to 24 h when the recipient mice were challenged immediately after transfer. Both MoAbs and complement treatment of the transferred cells demonstrated that the phenotype of the early response cells which elicited a response at 6 h after challenge was Thy1[sup +], B220[sup +], αβ TCR[sup ], γδ TCR[sup ], CD3[sup ], CD4[sup ], CD5[sup +] and CD8[sup ]. The in vitro treatment of effector cells with MoAbs against not only αβ TCR but also γδ TCR, together with complement, was found to diminish substantially the late response, elicited 12–24 h after challenge. γδ T cells reconstituted the ability of αβ T cells to transfer 24 h CHS responsiveness. The phenotype of the γδ T cells that assist CHS effector αβ T cells was CD3[sup +], CD4[sup ] and CD8[sup +] and these regulatory γδ T cells were neither Ag-specific nor MHC-restricted. Furthermore, γδ T cells from normal spleen could also assist αβ T cells in adoptive transfer of the 24 h CHS response in a non-MHC-restricted manner. RT-PCR demonstrated that αβ T cells strongly ex... [ABSTRACT FROM AUTHOR]