Generation of artificial lymphoid tissues and their application.

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We showed that our artificial lymphoid tissues possess not only basic structure of normal lymphoid tissue, but also immunologically important function of antigen specific antibody production. To construct "artificial lymphoid tissue" structures, a certain biocompatible material containing a thymus derived stromal cell line and cytokines was prepared, and transplanted to renal subcapsular space in mice. The accumulation of the lymphocytes was accelerated by the addition of bone marrow derived mature dendritic cells(DCs) in the graft along with the stromal cells at the time of transplantation.Many and relatively large T cell foci surrounded by B cell accumulation, which is similar to T cell and B cell area in secondary lymphoid tissues. Further immunohistochemical analysis revealed that the grafts with many T cell and B cell accumulation structurally resembled secondary lymphoid tissues in following aspects(points) ; 1)CD11c+ dendritic cells were found scattered both in T cell and B cell accumulation in the graft, 2)the CD4/CD8 ratio of T cells in the cluster was similar to that of T cell areas in normal lymph node tissues, 3)some of B cell clusters contained CR1 positive dendritic cells in the center, suggesting follicular dendritic network formation, 4)peanut agglutinin(PNA) positive B cells were detected in some of B cell clusters, 5)Syndecan-1 positive plasma cells were found around B cell accumulation, and 6)PNAd(peripheral node addressin) or MAdCAM-1(mucosal addressin cell adhesion molecule-1) positive HEV(high endothelial venule)-like structure was found in some of the grafts(especially) with many T cell and B cell accumulation.In addition, antigen specific antibody formation in the grafts was confirmed by enzyme-linked immunospot(ELISPOT) assay and immunohistochemical analysis.