Expression of thyroglobulin on follicular dendritic cells of thyroid mucosa-associated lymphoid tissue (MALT) lymphoma

Reportedly, thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Hashimoto's thyroiditis. However, it remains unknown which antigen is closely associated with thyroid MALT lymphoma. We examined whether B cell response to thyroglobulin (Tg), which is a common thyroid-specific autoantigen, is related etiologically to the pathogenesis of thyroid MALT lymphoma. Expression of human Tg antigens and Cluster of differentiation (CD) 35 was examined immunohistochemically in 15 cases of thyroid MALT lymphoma using paraffin-embedded, formalin-fixed tissue specimens. In all cases of thyroid MALT lymphoma, human Tg was detected immunohistochemically in the follicular epithelial cells and follicular dendritic cells (FDCs). These FDCs were positive by double immunostaining for anti-human Tg rabbit polyclonal antibody (Ab) and for CD35. Results showed that the Tg, a thyroid autoantigen, had immunostained the germinal center of the thyroid MALT lymphoma. The Tg was present in the FDCs, as revealed by the staining pattern of the germinal center;this fact was confirmed by double immunostaining of anti-human Tg mouse monoclonal Ab and anti-CD35 mouse monoclonal Ab. The results of our study suggest that Tg is an autoantigen that is recognized by thyroid MALT lymphoma cells.</p

Detection of HTLV-I pX Gene by Polymerse Chain Reaction Using Newly Designed Primers

Newly designed oligonucleotide primers, KI-7 and KI-8 for the human T cell lymphotropic virus type I (HTLV-I) pX gene were synthesized using an automated DNA synthesizer. Previously known HTLV-I-infected cell lines, MT-1 and MT-2, were used as positive controls and HTLV-I-uninfected cell lines, Molt-4, SBC-3, ABC-1, and EBC-1, as negative controls. Peripheral blood mononuclear cells from 17 patients with anti-HTLV-I antibody and 10 healthy individuals without anti-HTLV-I antibody were studied by polymerase chain reaction (PCR) with KI-7 and KI-8. All DNA samples from HTLV-I-infected cell lines and 17 patients with anti-HTLV-I antibodies showed positive signals of the HTLV-I pX gene. None of the DNA samples from HTLV-I-uninfected cell lines or 10 healthy individuals showed positive signals. When serially diluted DNA of MT-2 cells were amplified by 35 cycles of PCR, the detection limit of the pX gene by using the primer pairs was DNA from about 1.5 MT-2 cells. Specificity and detectable capacity of primer pairs, KI-7 and KI-8 were confirmed to be enough to use for the diagnosis of HTLV-I infection.</p

Detection of the pX gene of human T-lymphotropic virus type I in respiratory diseases with diffuse interstitial pulmonary shadows and lung cancer.

The presence of the HTLV-I gene in peripheral blood mononuclear cells was studied by polymerase chain reaction in 42 patients including 16 with lung cancer, 12 with diffuse panbronchiolitis (DPB), 11 with idiopathic interstitial pneumonia (IIP), and 3 with pneumoconiosis and hematological malignancy. Sequences equal to a part of the pX gene were found in 44% of the lung cancer cases, 50% of the DPB cases, 55% of the IIP cases, and 100% of the cases of pneumoconiosis and leukemia. In the lung cancer cases, detection of the pX gene was frequently associated with the existence of diffuse interstitial pulmonary shadows. The pX gene was detected in 100% of patients with anti-HTLV-I antibody, 50% of patients with HTLV-I-related reaction and 14% of patients who tested seronegative. It may be inferred from the results that respiratory diseases that produce diffuse interstitial pulmonary shadows are closely associated with HTLV-I infection and that the HTLV-I-related reaction to the immunofluorescent test might reflect the latent infection state of HTLV-I.</p

Overexpression of Interleukin-2 Receptor α mRNA in Pulmonary Lymphocytes of Lung Cancer Patients Associated with Interstitial Pulmonary Shadow

The activity of pulmonary lymphocytes was evaluated by the detection of interleukin-2 (IL-2) receptor alpha mRNA expression in lung cancer patients associated with diffuse interstitial shadow on roentgenograms of their lungs. Reverse transcription coupled with the polymerase chain reaction was used to detect mRNA expression. In 5 of 6 patients, IL-2R alpha mRNA expression was increased in pulmonary lymphocytes compared with 4 normal controls. The expression in this mRNA in peripheral blood lymphocytes was almost undetectable in either normal controls or these patients. These results suggest that pulmonary lymphocytes in patients with lung cancer associated with diffuse interstitial shadows are activated and may promote the inflammatory process generating pulmonary fibrosis

Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease

Chronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into OH model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplantation period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with GSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT