Bone marrow transplantation (BMT) is now a promising therapy for a variety of hematopoietic and immunodeficiency diseases that are otherwise impossible to treat effectively. Graft versus host reaction (GVHR) following BMT has been one of the major problems for immunologically incompetent recipients. However, GVHR has two different features. Minor GVHR prompts full replacement of recipient lymphoid tissues by donor cells which may lead to eradication of malignant cells in leukemia patients. On the other hand, GVHR results in immunological suppression and modification of T cell repertoire among donor derived lymphocyte population. The latter influence is mainly attributed to the agressive response of donor mature T cells against thymic stromal components that are involved in positive or negative selection of thymocytes.

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We investigated whether the administration of small-dose etoposide for a long period of time as a post intensive therapy is effective on remission duration and survival of patients with non-Hodgkin's lymphoma. After complete remission following CHOP or VEPA therapy, 33 patients were registered and administered etoposide at a daily oral dose of 25mg/body for a long time (median days; 211). Twenty-seven patients who were treated without the maintenance therapy, were used as a historical control.
The long-term complete remission ratio at 3 years was 54% for the etoposide group compared with 36% for the control group. Especially in patients over 65 years of age, the remission ratio was 61% for the etoposide group compared with 25% for the control group.
The long-term survival ratio at 5 years was 67% for the etoposide group compared with 59% for the control group. The small-dose etoposide as a post intensive therapy seemingly showed a beneficial effect but not statistically significant on the remission duration (P=0.08, Generalized Wilcoxon test) and the survival length (P=0.96, Generalized Wilcoxon test).
Side effects and abnormal laboratory findings were minimal in the etoposide group except one patient with leukopenia (grade 4).
These preliminary data suggested the usefulness of the small-dose etoposide as a post intensive therapy for treatment of non-Hodgkin's lymphoma.

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Here we study the precise localization of different eleven Ca²⁺ binding proteins in each five zone of lymphoid follicles by immunohistochemical and immunocytochemical stainings with special reference to the expression of these proteins on follicular dendritic cell (FDC). In results, the basal light zone among lymphoid follicles of lymphatic tissues such as tonsile, lymph node, appendix, and Peyer's patch was strongly labelled by calmodulin, caldesmon, calcineurin, calbindin-D, annexin II, annexin VI, and S-100 protein, suggesting that this zone is a site to be highly dependent upon Ca²⁺ ion. On the other hand, calretinin and migration inhibitory factor-related proteins (MRPs) 8, 14, and 8/14 were negative in lymphoid follicles. Immunocytochemically calmodulin and S-100 protein were positive on isolated FDCs. Interestingly, while caldesmon was positive on FDCs by immunohistochemical staining, it was negative on isolated FDCs. Immunoelectron microscopy demonstrated that caldesmon localized at the periphery of the cytoplasm of FDCs along twinning thick fibers, stress fibers. These data indicated that caldesmon takes part in formation and maintenance of the cytoskeleton of FDC in relation with actin.

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Lymphoid tissues are composed of B-cell dependent area (lymphoid follicle), and T-cell dependent paracortical and interfollicular areas. In lymphoid follicles, B lymphocytes and follicular dendritic cells (FDCs) play a central role of humoral immunity. B lymphocytes mature to memory B cells or plasmablasts through the proliferation in the dark zone (DZ), the selection in the basal light zone (BLZ), and the differentiation in the apical light zone (ALZ). In these processes, the importance of many cytokines has been pointed.There is, however, little information in the interature about the cytokine receptors in lymphoid follicles. The aim of our study was to investigate the localization of cytokines and theirreceptorsinhuman lymphoid tissues using immunohistochemical and immunocytochemical methods. FDCs were positive for transforming growth factor beta receptor type II (TGF-beta R II) in ALZ, interleukin 1 receptor type II (IL-1 R II, CD121a), interleukin 2 receptor beta (IL-2 R-beta, CD122), interleukin 4 receptor (IL-4R, CD124), interleukin 6 receptor (IL-6R, CD126), granulocyte macrophage-colony stimulating factor receptor (GM-CSF R, CD116w) in the BLZ and ALZ. Many cytokine inverstigated in this study were negative on FDCs except the TGF-beta, but positive on many T cells in lymphoid follicles.
Furthermore, we investigated the relationship between IgA positive plasma cells and the expression of TGF-beta and its receptor in lymphoid follicles. The data indicated that lymphoid follicles containing more IgA-positive plasma cells tended to be, simultaneously, more frequently labeled by TGF-beta and its receptor.
These data indicated that cytokines produced by T-cells not only may directly affect on B-cells, but also indirectly via FDCs expressing receptors for some cytokines. Simultaneous evaluation of both cytokines and their receptors may provide a powerful strategy of clarifying the cytokine network and transduction in lymphoid follicles.

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The expression of adhesion molecules on human tonsillar follicular dendritic cells (FDCs) in vivo on cryostat sections and in vitro on isolated FDCs on cytospin preparations was studied. Isolation of FDCs was performed using a magnetic cell sorter (MACS). Immunochemically, FDCs were positive for Mac-1 (CD11b), sialyl-Le^x (CD15s), CD22, integrin β1 (CD29), CD40, VLA-α3 (CD49c), VLA-α5 (CD49e), VLA-α6 (CD49f), ICAM-3 (CD50), ICAM-1 (CD54), B7 (CD80), and VCAM-1 (CD106). These adhesion molecules, except ICAM-3 (CD50) which was weakly positive only in the light zone (LZ), were positive with a lacy pattern in all zones of secondary lymphoid follicle, especially strong in the LZ. ICAM-3 (CD50) was positive on more than half of isolated FDCs, but other molecules were positive on almost all isolated FDCs. Concerning the ligands on B cells for these adhesion molecules, the Mac-1 (CD11b)-ICAM-1 (CD54), the ICAM-3 (CD50)-LFA-1 (CD11a/18), and the VCAM-1 (CD106)-VLA-4 (CD29/49d) interactions in the LZ, the sialy-Le^x (CD15s)-L-selectin (CD62L) and the VCAM-1 (CD106)-VLA-4 (CD29/49d) interactions in the mantle zone, and the ICAM-1 (CD54)-LFA-1 (CD11a/18) interaction in the entire lymphoid follicle may participate in FDC-B cell adhesion. Furthermore, above mentioned immunohistochemical evidence that FDCs were positive for fibronectin-receptor (CD29/CD49e) and laminin-receptor (CD29/CD49f), was confirmed with a frozen-section binding assay, using isolated FDCs and cryostat sections of tonsils. The numbers of FDCs binding to germinal centers (GCs) were reduced remarkably by pretreatment with monoclonal antibodies for CD29 (32.8±4.1% of the control), CD49e (29.7±2.5%), and CD49f (18.8±0.8%). These data clearly indicated that FDCs bind to the reticulin or laminin fiber in GCs via either receptor.

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