We have investigated the association of immunoescape mechanisms in nasopharyngeal carcinoma (NPC) lesions with EpsteinBarr virus (EBV) infection and clinical course of the disease. Tumor biopsy specimens obtained from 36 Japanese NPC patients were examined for antigen processing machinery component and HLA class I antigen expression, CD81 T cell infiltration, and Fas, Fas ligand (FasL) and IL-10 expression using immunohistochemical staining. The results were correlated with the histopathological characteristics of the lesions, the clinical course of the disease and EBV infection. LMP2, TAP1, tapasin and HLA class I antigens were downregulated in more than 65% of the lesions tested, while FasL, Fas and IL-10 were expressed in at least 60% of the lesions.

2 II. AbstractMacrolides are effective therapeutic agents for chronic respiratory tract diseases, such as chronic sinusitis, sinobronchial syndrome and diffuse panbronchiolitis. Although only limited information is available about their mechanisms, suppression of various inflammatory cytokines etc.) and some transcription factors has been reported to be involved. Non-typeable 3

Our present results indicate that these peptides would be candidates for a widely applicable peptide vaccine formulation.

P6 outer membrane protein is one of the candidates for a vaccine formulation against non-typeable Haemophilus influenzae (NTHi) infection. However, otitis-prone children who have recurrent episodes of acute otitis media due to NTHi fail to respond adequately to P6. An innovative approach to vaccination is therefore required to augment such children's immune response. To develop an effective peptide vaccine, we established P6-specific CD4(+) T-cell lines (TCLs) restricted by the human histocompatibility leukocyte antigen (HLA)-DR9 molecule, and revealed a human T-cell epitope on P6 and its core peptide sequence (p77-85; EYNIALGQR). Furthermore, we found that 3 analog peptides, E77D (the substitution of E at position 77 with D), N79G, and R85K, induced high proliferative responses as well as marked cytokine production when compared to the T-cell epitope peptide. These peptides may be candidates for a peptide vaccine formulation effective against NTHi infections, even in otitis-prone children.

Methotrexate (MTX) has been increasingly administered to patients with rheumatoid arthritis (RA), resulting in methotrexate-associated lymphoproliferative disorder (MTX-LPD) in patients. We reported three case of rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy who developed MTX-LPD. A 72-year-old woman treated with MTX since December 1997 (total dose 3684 mg) presented with swelling of the right tonsil in October 2006, and diffuse large B-cell lymphoma was diagnosed by tonsil biopsy and positive EBER1. When MTX therapy was interrupted, the tonsil was shrank and chemotherapy was not necessary. She followed a good clinical course for 12 months. Two other patients treated with MTX for RA for several years presented with enlarged neck lymph nodes and were diagnosed with MTX-LPD. Neck lymph nodes shrank upon MTX withdrawal in several weeks. There have been no signs of recurrence in these cases and they followed a good clinical course. The oncogenic potential of MTX and RA is reviewed.